KR20170093511A - Method and system for predicting risk of genetic disease in a putative offspring - Google Patents

Abstract

Provided are a method and system for predicting the risk of developing the genetic disease of putative offspring between a male subject and a female subject. The method and system according to one aspect can protect the privacy of individual genetic information, prevent or early diagnose future genetic diseases in children by deleting genetic information not related to genetic diseases for future children in the genomic information of men and women not to be disclosed to anyone. The method includes a step of obtaining genomic sequence analysis data, a step of extracting mutation, a check step, and a step of storing mutation information.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a method and system for predicting the risk of developing a genetic disease of an estimated offspring,

To a method and system for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject. And a computer-readable recording medium storing a program for realizing the method.

Human genome research has received a great deal of attention from the fact that the sequence of human genes has been revealed by the human genome project. The advancement of technology has speeded up the reading of the entire genetic sequence, and the cost has also declined to the point of reach of the general public. As a result, the number of individuals who are interested in genetic counseling is increasing, such as predicting the types of diseases that can occur in a person or family through genetic testing and the risk of developing a specific disease. In particular, men and women planning their children can predict the risk of future genetic disease by their genetic analysis. In particular, in the case of recessive genetic diseases, it is mostly caused by the parents of the donor. Since the dominant genetic diseases such as cancer are manifested as symptoms and can be cured at the early treatment, genetic diseases can be diagnosed early, Prevention is important. Therefore, it is desirable for men and women planning for their children to be able to anticipate the possibility and risk of genetic diseases for future children so that they can prepare more actively.

However, in the case of conventional disease-predicting genetic testing methods, the presence of specific genes or mutation information of parents not related to genetic diseases of children are disclosed. This can be a problem in the protection of individual privacy and social discrimination. Furthermore, since certain genetic disorders depend on the genetic predisposition of both parents, even if one parent has a specific gene mutation as a bearer of this genetic disorder, the genetic disorder may not be present in offspring, Analysis shows that the person and the other person can react sensitively to the fact that it is known to be a person with a genetic mutation, and the person can be subject to social discrimination from the moment when such fact is known. As such, it is impossible to pick up known information even if it is genuinely meaningless genetic information that does not cause a genetic disease to the child of the future as well as future children, and genetic testing should be approached carefully . Therefore, an examination method that can predict the risk of genetic diseases in future children is required while thoroughly protecting individual privacy related to genetic information.

Estimates between male and female subjects that reveal genetic information that is at risk of developing a hereditary disease of the estimated offspring without disclosing genetic variation information that is not related to the occurrence of the genetic disease of the future in male and female subjects with a child plan And a method and system for predicting the risk of offspring genetic disease outbreak.

One aspect includes (a) obtaining genomic sequence analysis data of a male subject and a female subject; (b) obtaining genomic sequence analysis data of male and female subjects through mapping of genomic sequence analysis data and standard nucleotide sequence of a subject selected randomly among the two subjects; Extracting mutations from the genomic sequence analysis data of each object through mapping with a standard nucleotide sequence; Confirming whether the extracted mutation is associated with autosomal recessive genetic disease; If the mutation is associated with an autosomal recessive disorder, determining whether the mutated gene has a mutation associated with an autosomal recessive inherited disorder in both of the subjects; And storing mutation information of each subject for the gene if both genes in the gene have a mutation associated with autosomal recessive genetic disease. Provides a way to predict risk.

The method of predicting the risk of genetic disease of the presumed offspring of the present invention is to provide information necessary for predicting the genetic disease outbreak of future children between men and women, Or " a method for preventing genetic disease in a progeny offspring ". The term "prediction " refers to determining whether a genetic disease is likely to occur in future offspring, or whether the likelihood of genetic disease is relatively high. The method can be used to prevent the occurrence of a genetic disease patient, or to diagnose a child's genetic disease early, while protecting the genetic information from a premarital couple or a couple planning a child.

The term "subject" refers to all animals classified as mammals and may include, for example, humans, non-human primates, cows, horses, pigs, sheep, goats, dogs, cats or rodents. Specifically, the object may be a human of any age or race.

The method for predicting the risk of developing a genetic disease of a progeny offspring between a male subject and a female subject according to this aspect can be performed by one or more processors. The term "processor" is an apparatus for processing a plurality of mutation information related to genome sequence analysis data of an object performed by an experimenter, and can classify or delete a plurality of mutation information input into a database by an experimenter . The processor may be, for example, a computer processor. When the method is performed by a computer processor, the method is also referred to as a 'computer-implemented identification method of estimating the risk of genetic disease outbreak of a progeny between a male and a female subject' .

In a method according to this aspect, the genetic disorder may be an autosomal recessive genetic disorder. The autosomal recessive inherited diseases include, for example, Wilson disease, Glycogen Storage Disease I, Phenylketonuria, Gitelman syndrome, Cystic Fibrosis , Autosomal Recessive Congenital Hearing Impairment, Primary Congenital Glaucoma, Ataxia Telangiectasia, or Congenital Hypothyrodism may be included.

The method includes obtaining genomic sequence analysis data of a male subject and a female subject. The genomic sequence analysis data may be exome sequence data, whole genome sequence data, or sequence data of genes known to be associated with the disease. The term "exome" refers to all parts of the DNA sequence that contain the structural information of the protein, and may refer to all genomic regions except the intergenic region and the intron. The term "full-length genome ", also referred to as the total genome, refers to the entirety of DNA bases that store genetic information of a species.

The genomic sequence analysis data of each object can be retrieved from the database stored in the processor. The database may store genome sequence analysis data of a plurality of objects. Obtaining of the genome sequence analysis data of each of the above objects can be obtained experimentally. Specifically, the genome sequence analysis data of the subject can be obtained by extracting the nucleic acid from the biological sample derived from each subject and performing sequencing. The term "biological sample" refers to a biological sample of an animal that has been extracorporeally separated and refers to blood, plasma, serum, urine, cells, hair or tissue samples. Specifically, the biological sample may be blood collected from a subject. The sequencing may be specifically performed by next generation sequencing (NGS).

The method includes extracting mutations from the genomic sequence analysis data of the two obtained subjects. The term " mutation extraction "means identifying and / or discriminating information on the substitution, addition or deletion of nucleotides in the nucleotide sequence constituting the exon of the gene of interest. The substitution, addition, or deletion of such nucleotides can occur for a variety of reasons, for example, due to structural differences, including mutations, deletions, deletions, duplications, inversions and / or translocations of chromosomes. The mutation extraction can be performed by mapping the genomic sequence analysis data to a standard nucleotide sequence. The mapping of the genomic sequence analysis data to the standard nucleotide sequence means the operation of comparing the genomic nucleotide sequence with the standard nucleotide sequence. The term "reference neucleotide sequence" may refer to a genomic sequence that does not contain a mutation that is referenced for mutation confirmation. For example, a human nucleotide sequence, specifically NCBI37.1 or UCSC hg19 (GRCh37), published in the database of the National Institute of Bioscience and Biotechnology Information (NCBI) under the National Institutes of Health may be used as the standard sequence. A comparison between the nucleotide sequence of the genomic DNA and the standard nucleotide sequence can be performed using various known sequence comparative analysis programs such as Maq, Bowtie, SOAP, and GSNAP.

After the difference between the target and the standard nucleotide sequence is found through the mapping, reliable mutation information is extracted, and the extracted mutation information is compared with the existing database to determine whether the mutation affects the amino acid change or the protein structure It is possible to perform annotation for prediction. In this case, it is possible to proceed with the next step after performing the mutation information extraction and annotation for all the leads, or after extracting and annotating the mutation information for one lead, and then proceed to the next step. For example, Exome Aggregation Consortium (http://exac.broadinstitute.org/), Exome Variant Server (http://evs.gs.washington.edu/EVS) 1000 Genome Project (http://browser.1000genomes.org), dbSNP (http://www.ncbi.nlm.nih.gov/snp), or dbVar (http://ncbi.nlm.nih.gov/dbvar). Can be used.

The method for predicting the risk of developing a genetic disease of the estimated offspring includes a step of determining whether a mutation extracted from each of the subjects is related to an autosomal recessive inherited disease. The variation extracted from each object may be one or more. Confirming whether a mutation extracted from each of the above-mentioned subjects is associated with an autosomal recessive inheritance disease, specifically verifying whether the mutation exists in an autosomal recessive inheritance disease gene; If the mutation is in an autosomal recessive disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And, if the mutation does not correspond to a polymorphism, determining whether the mutation corresponds to a known mutation or etiology. In order to determine whether mutations extracted from each of the above subjects are associated with autosomal recessive diseases, for example, ClinVar (http://www.ncbi.nlm.nih.gov/clinvar), OMIM (http://www.ncbi.nlm.nih.gov/clinvar) .omim.org), the Human Gene Mutation Database (http://www.hgmd.org), or the Leiden Open Variation Database (http://www.lovd.nl).

Determining whether the mutation is present in an autosomal recessive disease gene means determining whether the mutation was found in a gene responsible for autosomal recessive genetic disease. More than 1,139 autosomal recessive genetic diseases are known. The gene responsible for the autosomal recessive inheritance disease, which is the basis for the above confirmation, includes all genes known to cause all known autosomal recessive inheritance diseases, or a gene known to cause a serious disease among them, (PMID: 21228398, 26354092, 26334176, 22170460). For example, OMIM, Sci Tranl Med 2011; 3: 65ra4 (PMID: 21228398) or PLoS Curr 2012 to confirm whether the mutation is present in the causative gene of autosomal recessive genetic disease. e4f9877ab8ffa9 (PMID: 22872815).

The step of ascertaining whether the mutation corresponds to a polymorphism that does not lead to the disease can be performed when the mutation is confirmed to be present in an autosomal recessive disease gene. The term "polymorphism" refers to an individual difference in the base sequence present on such a genome, in which there is a case where a base in an entire genome differs from one chromosome to another. Polymorphisms can cause differences in human traits regardless of disease, or can be a cause of disease. Polymorphism database (dbSNP), Exome Aggregation Server (ExAC), and / or Korean Reference Genome Database (KRGDB) can be used to determine polymorphism.

The step of ascertaining whether the mutation corresponds to a known mutation or pathogenic is performed when the mutation does not correspond to a polymorphism. In order to confirm whether the mutation corresponds to a known mutation, the Human Gene Mutation Database (HGVS), ClinVar, and / or mutation database for each disease or gene may be used. For information on how to determine whether the mutation is pathogenetic, refer to the American College of Medical Genetics (ACMG) and the Association for Molecular Pathology (AMP) published in the United States and the Standards and Guidelines for the Interpretation of Sequence Variants. (PMID 25741868).

As a result of checking whether the mutation of each object is related to autosomal recessive inheritance disease, the information about the mutation is deleted when mutation of each object is not related to autosomal recessive inherited disorder. That is, mutation information of each object not associated with autosomal recessive genetic disease is deleted. The 'deletion' means that all information related to a variation having an object is discarded and / or removed so that it is not disclosed to anyone including the object, the examiner, and the analyst. Specifically, when the mutation of each of the above objects does not exist in an autosomal recessive disease gene, or corresponds to a polymorphism that does not cause disease, or is not a known mutation and does not correspond to a pathogenicity, information on the mutation is deleted. Since the mutation information not related to the autosomal recessive inheritance disease is deleted, the mutation information is not disclosed to anyone, so that the privacy of each object can be protected.

When the mutation of each object is related to autosomal recessive inheritance disease, the mutation of each object is related to autosomal recessive inheritance disease. As a result, To determine if it has a mutation associated with a recessive genetic disorder. Mutations related to autosomal recessive genetic diseases of both of the above subjects may be the same or different. The confirmation step may be performed, for example, by discriminating whether or not the genes are the same by checking the genes of the respective objects on which mutations that are not deleted are related to the autosomal recessive inheritance disease.

The method comprises the steps of storing information on mutations associated with autosomal recessive genetic diseases of each of the subjects found in the gene when the mutated gene has a mutation associated with autosomal recessive genetic disease in both male and female subjects . For example, if mutated genes are found by comparing the genes of each subject in which mutations are associated with autosomal recessive genetic diseases, the mutation information of two subjects present in the same gene can be stored. The variation information may include, for example, the kind of the mutation, the position of the mutation, the genetic information in which the mutation exists, or information on the genetic disease caused by the mutation. The method may delete information about the mutation if the mutated gene does not have mutations associated with autosomal recessive genetic disease in both of the two subjects. In other words, the corresponding mutation information of the mutant gene related to the autosomal recessive genetic disease existing in only one object can be deleted.

The method may further include verifying the validity of the stored variation information. The verification step may be performed after determining that both of the two subjects have a mutation related to autosomal recessive inherited diseases in the gene in which the mutation is found. For example, the verification step may be performed before or after storing information on the variation of each object. If the verification step is performed before storing the mutation information of each object, only the mutation information determined to be valid in the verification step is stored, and invalid mutation information is deleted. When the verification step is performed after storing the mutation information of each object, the mutation information determined to be invalid in the verification step is deleted. The verification may be for verification of the nucleotide sequence analysis result of the gene in which the mutation information is stored. The verification of the nucleotide sequence analysis result of the gene in which the mutation information is stored may be performed by, for example, confirming that the mutated mutant is found by the polymerase chain reaction, microarray analysis or Sanger sequencing method. In addition, the above verification may be performed by performing a bioinformatic analysis to determine the pathogenicity, and may be performed by reconfirming a mutation / polymorphism database and the like. As a result of the verification, if the stored variation information is invalid, the stored variation information is deleted.

In addition, the method may perform a step of verifying validity of the mutation information before storing the mutation information. That is, if the gene in which the mutation is found has a mutation related to an autosomal recessive inherited disease in both the male and female subjects, the mutation of the corresponding gene in the male and female subjects is subjected to the verification of the nucleotide sequence analysis result of the gene . Verification is as described above. When the result of the verification is that all the nucleotide sequence analysis results on the mutation of each object are valid, the information on the mutation is stored, and if it is invalid, the information on the mutation is deleted.

The method may further include calculating an onset risk of genetic disease associated with the stored variation information of the estimated offspring based on the total stored variation information. For example, if two couples in the same gene are found to have one known mutation or a mutation in the pathogenicity, their putative offspring can have a 25% chance of autosomal recessive genetic disease associated with that mutation , And the probability may be expressed as a risk. Also, the risk may be a score obtained by scoring the probability according to certain criteria and various factors. For example, the risk may be scored based on factors such as the probability of disease occurrence, race, sex, diet, and / or lifestyle when the probability of genetic disease is mutated.

The method may further comprise displaying the total stored variation information. In one embodiment, the displaying step displays the stored variation information when the stored variation information is present, and when the stored variation information does not exist, for example, 'no risk of developing autosomal recessive genetic disease' or ' not detected 'or the like. The step of displaying the stored mutation information may be specifically indicated as the presence or absence of a genetic disease associated with the total stored mutation and the risk thereof. When expressed as a risk, for example, a 'positive' indication of the disease associated with the stored variation, as well as a risk score calculated in the risk calculation step, may be displayed.

The method may further comprise providing the entity with a report containing the total stored variation information. The report may include the risk of developing a genetic disease of the estimated offspring calculated. The report may include information about the mutation (for example, the location of the mutation, the characteristics of the specific mutation, the mutation and the genetic name discovered), and the risk of developing the genetic disease depending on the selection of the object. The report can be printed, stored on a computer, viewed online, or viewed on an app. The report may be accessible via an information portal, an online portal, which can be easily accessed by the entity using a computer, an Internet web site, a telephone, or other means enabling similar access to information. An online portal can be a secure online portal or a web site.

Hereinafter, the method for predicting the risk of genetic disease outbreak of a progeny according to one aspect of the present invention and the method, medium, and system according to another aspect of the present invention will be omitted in order to avoid the excessive complexity of the present specification. Also mentioned in the description of the claimed composition among the terms and elements mentioned in methods, media and systems according to another aspect of the invention is a method for predicting the risk of developing a genetic disease of a putative offspring according to the above aspect And the contents common to methods, media, and systems according to other aspects below omit duplicate descriptions thereof in order to avoid the excessive complexity of the present disclosure. It is also to be understood that what is mentioned in the description of the terms and elements mentioned in the methods, media and systems according to other aspects below is as set forth in the description of the method according to this aspect.

Other aspects include: a) obtaining genomic sequence analysis data of male and female subjects; b) extracting mutations from the genomic sequence analysis data of each subject through mapping with standard sequence; c) determining whether a mutation found in one of the extracted mutations is associated with autosomal recessive genetic disease; d) if the mutation found in the subject is associated with an autosomal recessive disorder, determining whether the other subject has a mutation in the gene of interest associated with the autosomal recessive disorder; e) if the other subject has a mutation in the corresponding gene, determining whether the mutation of the other subject is related to autosomal recessive inherited diseases; And f) storing mutation information of each subject for the gene if the mutation of the other subject is related to autosomal recessive genetic disease. Provides a method to predict the onset risk.

In this method, the genetic disorder of the putative progeny may be an autosomal recessive genetic disease. The above-mentioned autosomal recessive genetic diseases are as described above.

The method comprising the steps of: a) obtaining genome sequence analysis data of a male subject and a female subject; And b) extracting mutations from the genomic sequence analysis data of the respective subjects through mapping with the standard nucleotide sequences are as described above.

The method comprises extracting mutations from the genomic sequence analysis data of each subject and then determining whether the mutation found in an arbitrarily selected subject of the two subjects is associated with autosomal recessive genetic disease. The variation found in the subject may be one or more. The arbitrarily selected object may be a male object or a female object, and specifically, it may be a female object. Confirming whether a mutation found in the subject is related to an autosomal recessive genetic disorder comprises the steps of: confirming whether the mutation is present in an autosomal recessive genetic disease gene; If the mutation is in an autosomal recessive disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And, if the mutation does not correspond to a polymorphism, determining whether the mutation corresponds to a known mutation or etiology. Each step is as described above.

If the mutation found in the subject is not related to autosomal recessive inheritance, the information about the mutation is deleted. That is, information about mutations found in a subject not associated with autosomal recessive genetic disease is deleted. Specifically, when the mutation found in the above-mentioned subject does not exist in the gene of autosomal recessive disease gene, corresponds to a polymorphism that does not cause disease, or does not correspond to a known mutation and does not correspond to a pathogenicity, the mutation information is deleted.

The method comprises the steps of: if the mutation found in the subject is associated with autosomal recessive inheritance disease, confirming that the other subject has a mutation in the gene of interest associated with the autosomal recessive inherited disorder found in the subject Can be performed. The mutation of the other object may be the same as or different from the mutation found in one subject. Whether or not the other subject has a mutation in the corresponding gene can be confirmed, for example, by checking whether the gene in which the mutation of the other subject extracted in the mutation extracting step is the same as the mutation gene related to the autosomal recessive inheritance disease of the subject Lt; / RTI > Or mutation information extraction and / or annotation processing is performed on a lead mapped to a gene in which mutation related to autosomal recessive genetic disease is found in the above-mentioned subject, after mapping the genome sequence leader to the standard nucleotide sequence from the genome sequence analysis data of another subject It can be done through a swap. If another subject does not have a mutation in the gene of interest associated with an autosomal recessive genetic disorder found in one subject, the information about the mutation associated with the autosomal recessive genetic disorder found in the subject is deleted.

The method may further comprise the step of verifying whether the mutation of the other subject is associated with an autosomal recessive inherited disorder when the other subject has a mutation in the corresponding gene of a mutation associated with an autosomal recessive genetic disorder found in a subject do. Determining whether the mutation of the other subject is associated with autosomal recessive genetic disease comprises the steps of: determining whether the mutation corresponds to a polymorphism that does not cause the disease; And, if the mutation does not correspond to a polymorphism that does not lead to the disease, checking whether the mutation corresponds to a known mutation or etiology. The method deletes the mutation information if the mutation of the other object corresponds to a polymorphism that does not cause autosomal recessive inheritance or does not correspond to a known mutation and does not correspond to a mutation. Here, the mutation information may be mutation information related to the autosomal recessive inheritance disease of the subject and / or mutation information of the other object.

In this method, when the mutation of the other object corresponds to a known mutation or a disease-afflicting mutation, information on mutation of each object present in the gene is stored.

The method may include a method in which each step of steps c) to f) is completed for all the mutations extracted from one object, and then the method proceeds to the next step, or a method of selecting an arbitrary mutation from a mutation extracted from one object, It is possible to sequentially perform steps c) to f). The manner in which the steps c) to f) are sequentially performed for each of the mutations selected by selecting the arbitrary mutation is determined by performing the steps c) to f) for any selected mutation, step f) is performed so that steps c) through f) are performed on all the mutations extracted from one subject. When the mutation of the arbitrarily selected one of the objects is not related to the autosomal recessive genetic disease in the manner in which the mutation is sequentially selected and the steps c) to f) are sequentially performed for each mutation, Or when the mutation of the other subject is not related to the autosomal recessive inheritance disorder, the mutation information is deleted, and the mutation information immediately after c ) To f) may be performed.

In one embodiment, the method according to which the c) to f) step is performed sequentially by selecting the arbitrary mutation and for each mutation is characterized by comprising the steps of: (a) obtaining genome sequence analysis data of a male subject and a female subject; (b) extracting mutations from the genomic sequence analysis data of the two subjects through mapping of the genomic sequence analysis data of the two subjects to the standard nucleotide sequence; (c) selecting any of the mutations of one subject; (d) confirming whether said arbitrary mutation (first mutation) is associated with autosomal recessive genetic disease; (e) if the first mutation is associated with an autosomal recessive genetic disorder, determining from the genomic sequence analysis data of the other subject whether the first mutation has a first mutation or a first mutation in the gene in which the first mutation is found ; (f) if the other subject has a first 'mutation in the gene in which the first mutation is found, checking whether the first' mutation corresponds to a known mutation or etiology; (g) storing the first variation and the first variation information of each object if the first variation corresponds to a known mutation or etiology; And (h) performing the steps (c) through (f) for the next arbitrary mutation (second mutation) among the mutation information extracted in the step (b).

And may include a step of selecting any one of the variations of one object in the above embodiment. The first variation may mean the first randomly selected variation among the extracted variations.

In one embodiment, if the first mutation is associated with a recessive genetic disorder, it may be determined from the genomic sequence analysis data of the other subject whether the first mutation has a first mutation or a first mutation in the gene in which the first mutation was found . The first 'mutation means a mutation other than the first mutation found in the gene in which the first mutation is found.

(G) 'instead of steps (f) and (g) when the other object has a first variation as a result of checking in step (e) can do. The subsequent step (h) is performed in the same manner.

In one embodiment of the present invention, the step of storing the first variation information and / or the first variation information of each object further comprises the step of, for the second variation of the mutation information extracted from the genome sequence analysis data of the object, Each corresponding step can be performed in the same manner. The second variation may be a variation selected from among the extracted variation except for the first variation. When the execution of the corresponding step for the second variation is completed, each of the corresponding steps can be performed for the third variation arbitrarily selected among the remaining variation, and finally, all the steps extracted from the genome sequence analysis data of the object Each corresponding step can be sequentially performed on the variation.

The method according to another aspect may further include verifying that the stored variation information is valid. The verification step may be performed after it is determined that the mutation of the other object corresponds to a known mutation or a variable mutation. For example, the verification step may be performed before or after storing information on the variation of each object. If the verification step is performed before storing the mutation information of each object, only the mutation information determined to be valid in the verification step is stored, and invalid mutation information is deleted. When the verification step is performed after storing the mutation information of each object, the mutation information determined to be invalid in the verification step is deleted.

The method may further include calculating an onset risk of genetic disease associated with the stored variation information of the estimated offspring based on the total stored variation information.

The method may further include displaying the total stored variation information.

The method may further comprise providing the entity with a report containing the total stored variation information.

The steps of verifying, calculating the risk of developing a genetic disease, displaying, and providing the report to the individual are as described above.

Another aspect includes obtaining genomic sequence analysis data of a female subject; Extracting a mutation from the genome sequence analysis data of the female subject obtained through mapping with a standard nucleotide sequence; Confirming whether the extracted mutation is associated with a sex chromosomal recessive genetic disorder; And storing the mutation information if the mutation is related to a sex chromosomal recessive inheritance disorder and deleting the mutation information if the mutation is not associated with a sex chromosomal recessive inheritance disorder. Provides a way to predict risk.

In a method for predicting the risk of developing a genetic disease of an estimated offspring according to the other aspect, the genetic disease may be a sex chromosomal recessive genetic disease. Such sexually transmitted diseases include, for example, Duchenne Muscular Dystrophy, Hunter Syndrome, Hemophilia, Adrenoleukodystrophy, Menkes Disease and the like .

The method extracts genomic sequence analysis data mutation information of a female subject to predict the risk of developing sex chromosomal recessive genetic diseases of the estimated offspring. The step of obtaining the sequence analysis data in the above method and the step of extracting the mutation information are as described above.

In this method, it is confirmed whether the extracted mutation is associated with a sex chromosomal recessive genetic disorder. Confirming whether the mutation is present in a sex chromosomal recessive disease gene; If the mutation is in a recessive genetic disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And, if the mutation does not correspond to a polymorphism that does not lead to the disease, checking whether the mutation corresponds to a known mutation or etiology.

The method may further comprise storing information about the mutation if the extracted mutation is associated with a sex chromosomal recessive inheritance disorder and deleting the mutation information if the mutation is not associated with a sex chromosomal recessive inheritance disorder . In other words, information on extracted mutations of female subjects not related to sex chromosomal recessive genetic diseases can be deleted.

The method may further include the step of verifying that the result of the nucleotide sequence analysis of the gene in which the mutation information is stored in the female subject is valid when the mutation information is stored. In addition, if the mutation is related to a sex chromosomal recessive disorder, the method may further comprise verifying that the result of the nucleotide sequence analysis of the gene associated with the mutation information is valid before storing the mutation information. As a result of the verification, when the nucleotide sequence analysis result of the gene associated with the mutation information is valid, the mutation information is stored, and if not valid, the mutation information is deleted.

In one embodiment, the method according to the other aspect is a method for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject, comprising the steps of: (a) obtaining genome sequence analysis data of a female subject; (b) extracting mutation information from the genome sequence analysis data of the obtained female subject through mapping with a standard nucleotide sequence; (c) determining whether the first mutation of the extracted mutation information is related to a sex chromosomal recessive disorder; (d) if the first mutation is associated with a sex chromosomal recessive genetic disorder, storing the first mutation information, and if the first mutation is not associated with a sex chromosomal recessive genetic disorder, ; And (e) performing the steps (c) to (d) for the second variation of the mutation information extracted in the step (b). In one embodiment, after the first variation is stored or deleted, the corresponding steps performed on the first variation for the second variation may be performed identically, and for each of the finally detected variations, .

The method may further include calculating an onset risk of the genetic disease associated with the stored variation information of the estimated offspring based on the total stored variation information. For example, if it is confirmed that a female subject has one known mutation or disease-affinitive mutation, the male offspring may have a sex-chromosomal recessive genetic disorder related to the mutation at a probability of 50% The probability may be scored by the user.

The method may further include displaying the total stored disparity information result. The method may further comprise providing the entity with a report containing the total stored variation information. The steps of calculating the risk of developing the genetic disease, displaying the gene, and providing the report to the subject are as described above.

Another aspect includes obtaining genomic sequence analysis data of a male subject and a female subject; Extracting mutations from the genomic sequence analysis data of each object through mapping with a standard nucleotide sequence; Determining whether the extracted mutation is associated with a treatable or preventable dominant genetic disease; And storing the mutation information if the mutation is related to a dominant genetic disease treatable or preventable and deleting the mutation information if the mutation is not related to a genetic disease that can be treated or prevented Provides a method to predict the risk of genetic disease.

In a method for predicting the risk of developing a genetic disease of an estimated offspring according to the another aspect, the genetic disease may be a dominant genetic disease. Specifically, the genetic disease may be a dominant genetic disease that can be treated or prevented. The preventable or treatable autosomal dominant genetic disease may include diseases allowed for each country and may include common genes related to dominant genetic diseases depending on the race or ethnicity of the subject, can do. The therapeutic or preventable dominant genetic diseases include, for example, Hereditary Breast and Ovarian Cancer, Hereditary Colorectal Cancer, Familial Adenomatous Polyposis, or Romano-Ward Syndrome (Romano-Ward Syndrome) and the like (PMID: 23788249). In one embodiment, the method discloses only the risk of developing a preventable, early diagnosis, treatment, and management of the disease due to the disclosure of the disease without treatment, It can reduce the morbidity and mortality of the subject's disease.

The method includes extracting mutation information from each of genome sequence analysis data of a male subject and a female subject through mapping with a standard nucleotide sequence. It is preferable that the above method extract mutation information from both male and female subjects.

The method includes the step of ascertaining whether the extracted mutation is associated with a treatable or preventable dominant genetic disease. Determining whether the extracted mutation is associated with a therapeutic or preventable genetic disease comprises the steps of: confirming whether the mutation is present in the gene for the dominant genetic disease that can be treated or prevented; If the mutation is present in the gene responsible for the dominant genetic disease, checking whether the mutation corresponds to a polymorphism that does not cause the disease; And, if the mutation does not correspond to a polymorphism that does not cause the disease, determining whether the mutation corresponds to a known mutation or etiology.

If the extracted mutation is related to a dominant genetic disease that can be treated or prevented, the information on the mutation is stored, and if the extracted mutation is not related to a genetic disease that can be treated or prevented, And deletes the information on the information. The polymorphism database, dbSNP, Exome Aggregation Server (ExAC), Korean Reference Genome Database (KRGDB), etc. can be used as the criteria for polymorphism. When the extracted mutation is not a polymorphism that does not cause the disease using such a database or the like, it is checked whether the mutation is a known mutation. If the extracted mutation corresponds to a polymorphism that does not cause the disease, . To check whether the mutation is known, use the Human Gene Mutation Database (HGVS), ClinVar, and mutation databases for each disease or gene. If the mutation is not a known mutation, it is checked whether it corresponds to the disease-specific mutation or VUS. If the mutation is a known mutation, information about the mutation is stored. Methods for determining whether the mutation is a disease-specific mutation or VUS are described in the American College of Medical Genetics (ACMG) and the Association for Molecular Pathology (AMP) published in the United States, including the "Standards and Guidelines for the Interpretation of Sequence Variants" You can refer to it (PMID 25741868). If the mutation is judged to be a disease-specific mutation or VUS, information on the mutation is stored.

In one embodiment, a method for predicting the risk of developing a genetic disease of a putative progeny according to the other aspect comprises the steps of: (a) obtaining genome sequence analysis data of a male subject and a female subject; (b) extracting mutation information from each of the genome sequence analysis data of the two subjects through mapping with a standard nucleotide sequence; (c) confirming whether the first mutation of the extracted mutation is associated with a dominant genetic disorder treatable or preventable; And (d) if the first mutation is associated with a dominant genetic disease treatable or preventable, storing information about the first mutation, and if the extracted mutation is not associated with a genetically curable or preventable disease, And discarding information about the first variation. In one embodiment, the treatment or preventable dominant genetic disease identification step performed for the first variation for the second variation after storage or deletion of information for the first variation may be performed in the same manner

The method may further include the step of verifying that the stored mutation result in the object having the stored mutation information is valid. The method may further include a step of verifying whether the result of the mutation information to be stored by the object is valid before storing the mutation information. For example, when the first variation information is valid, the first variation information is stored. If the first variation information result is not valid, the first variation information is not stored. .

The method may further include displaying the stored variation information.

The method may further include calculating an onset risk of the dominant genetic disease associated with the stored variation information of the estimated offspring based on the total stored variation information. The method may further comprise providing the entity with a report containing the total stored variation information. The steps of calculating the risk of developing the genetic disease, displaying the gene, and providing the report to the subject are as described above.

The method also describes the results to the subject, And performing genetic counseling including a preventive method and a therapeutic method.

The method for predicting the risk of developing a genetic disease according to one aspect of the present invention and the method for predicting the risk of developing genetic disease according to another aspect may be performed separately or in combination. For example, in a method for predicting the risk of developing a genetic disease of an estimated offspring according to one aspect, a mutation information extracting step from a genomic sequence analysis data of one subject is followed by selecting any mutation of the extracted mutation information, A genetic disease, a sex chromosomal recessive inherited disease, or a treatable or preventable dominant inherited disease. The subsequent steps can be performed according to each method.

Another aspect provides a computer-readable recording medium on which a program for realizing a method for predicting the risk of genetic disease outbreak of the estimated offspring is recorded.

The computer-readable recording medium may be a computer-readable recording medium. The computer readable recording medium includes all kinds of recording apparatuses in which data that can be read by a computer system is stored. Examples of the computer readable recording medium include a storage medium such as a magnetic storage medium (e.g., ROM, floppy disk, hard disk, etc.), optical reading medium (e.g., CD ROM, DVD, etc.). And may also be implemented in the form of a carrier wave (e.g., transmission over the Internet). The computer-readable recording medium may also be distributed over a network-connected computer system so that the computer-readable code can be stored and executed in a distributed manner.

Another aspect includes a receiving unit for receiving genome sequence analysis data of a male subject and a female subject; An information extracting unit for extracting mutation information from the genome sequence analysis data of each object through mapping with a standard nucleotide sequence; An analysis unit for determining whether the extracted mutation is related to a genetic disease; And a storage unit for storing the variation information. The present invention provides a system for predicting a genetic disease risk of an estimated offspring of a male subject and a female subject.

The genetic disease in the system may be an autosomal recessive inherited disorder, a sex chromosomal recessive inherited disorder, and / or a treatable or preventable dominant inherited disorder. Specifically, it may be an autosomal recessive inherited disease.

The system includes a receiving unit, an information extracting unit, an analyzing unit, and a storing unit. The receiving unit may receive the genome sequence data of the male subject and the female subject. The mutation information extracting unit can extract the mutation information from the genome sequence data of the object. The analysis department can determine whether the extracted mutation is related to a genetic disease. The analysis unit may include, for example, a first analyzing unit for checking whether the extracted mutation is associated with autosomal recessive inheritance disease; A second analyzing unit for verifying whether another subject has a mutation in the gene in which the mutation is found from genome sequence analysis data of another subject when the mutation is related to a recessive genetic disease; And a third analyzing unit for verifying whether the mutation of the other object corresponds to a known mutation or etiology when the other object has a mutation in the gene in which the mutation is found. Whether or not the extracted mutation is related to genetic disease is as described above. The first variation related information is stored in the storage unit when the variation of the other object in the third analysis unit corresponds to a known mutation or etiology. The first mutation-related information may include, for example, information about a first mutation extracted from an object, information about a genetic disorder caused by the first mutation, and / or a first mutation identified in another object Gene mutation information of genetic diseases, and the like.

In addition, the system may further include a verifying unit for verifying the validity of each mutation when the causative mutation of the autosomal recessive genetic disease is found in the two subjects and the mutation or the mutation of the mutation is finally confirmed. The system may further include an output unit for calculating a risk of developing a genetic disease associated with the stored mutation. The system may further include a display unit for reporting a risk level. Validation of variability, risk calculation, and risk reporting in the system are as described above.

Methods and systems according to aspects of the present invention can protect the privacy of an individual's genetic information because genetic information not related to the genetic disease of the future child is deleted from the genetic information of male and female, To prevent or early diagnosis of future genetic diseases of children.

Figure 1 is an overall schematic diagram of a method for predicting the risk of autosomal recessive genetic disease in an offspring according to one embodiment.
Figure 2 is a flow chart of a method for predicting the risk of autosomal recessive genetic disease in a progeny according to one embodiment.
Figure 3 is a flow chart of a method for predicting the risk of autosomal recessive genetic disease in a progeny according to another embodiment.
Figure 4 is a flow chart of a method for predicting the risk of autosomal recessive genetic disease in a progeny according to another embodiment.
FIG. 5 is a flowchart of a method for predicting the risk of autosomal recessive genetic disease in a progeny according to one embodiment.
Figure 6 is an overall schematic diagram of a method for predicting the risk of sex chromosomal recessive genetic disease in an offspring according to one embodiment.
7 is a flow chart of a method for predicting the risk of a sex chromosomal recessive inheritance disorder in an offspring according to one embodiment.
FIG. 8 is a flowchart of a method for predicting the risk of a sex chromosomal recessive inheritance disease of an estimated offspring according to an embodiment.
Figure 9 is an overall schematic diagram of a method for predicting the risk of treatment or preventable dominant genetic disease of the estimated offspring according to one embodiment.
10 is a flow chart of a method for predicting the risk of treating or preventing a progeny of a putative progeny according to one embodiment.
11 is a flowchart of a method for predicting the risk of a dominant genetic disease that can be treated or prevented in an offspring according to one embodiment.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1 will be described in detail through the embodiments of the invention below autosomal heat future children. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1. Estimation of risk of autosomal recessive inherited diseases in future children

1.1. Obtain nucleotide sequence data from prospective parents

Three pairs of couples visited the Samsung Medical Center (Seoul, Korea) genetic clinic to predict the possibility of future genetic diseases. All of these couples did not develop any specific disease and had normal phenotype. From the above-mentioned couples, a description was made of a prediction test for the risk of genetic disease outbreak of the offspring, and after obtaining the consent, a blood sample was taken to obtain exon base sequence data. However, the first couple agreed to examine only the possibility of autosomal recessive genetic disease, the second agreed to examine the possibility of autosomal recessive genetic disease and sex chromosomal recessive genetic disease, and the third couple Autosomal recessive genetic disease, sex chromosomal recessive genetic disease, as well as the possibility of developing a dominant genetic disease that can be cured or prevented. Exon sequence data were captured using the Agilent SureSelect Human All Exon v4 (Agilent Technologies, Santa Clara, Calif.) And analyzed using the Illumina HiSeq2000 platform (Illumina, San Diego, Calif.).

1.2. Detection and analysis of mutations related to autosomal recessive genetic diseases

Upon receipt of the obtained nucleotide sequence data, the possibility of developing an autosomal recessive genetic disease among the genes related to Mendel's genetic disease of a future child was analyzed for the first couple according to an aspect of the present invention. First, we selected female exome sequence data as a subject to extract mutation information. The following information was used for mapping, mutation information extraction and annotation. NGSQCToolkit v2.3.3 was used to perform quality control of ExQ sequence data in the form of FastQ file, and genome mapping was performed using the BWA-MEM algorithm. We used Picard v1.114 to exclude Duplicate data (MarkDuplicates) and perform the FixMate process (FixMateInformation). Re-alignment is performed using GATK v3.2-2 RealignerTargetCreator and IndelRealigner, and base quality recalibration process is performed using GATK BaseRecalibrator. The variant quality recalibration procedures for genotyping and variant filtering were performed using the HaplotypeCaller and VariantRecalibrator of GATK, respectively, and sensitivity was 99.7. Gene annotation was performed using an in-house custom-made script, and dbSNP build 141 and HGMD 2015.3 Professional version were used for annotation.

First, mutations which are not coding regions for proteins and which do not affect functions such as exon splicing or gene expression were immediately deleted in the analysis process, and the protein coding region base mutations were analyzed one by one. In order to effectively categorize possible candidate gene mutations, mutations already listed as disease-related mutations in HGMD (http://www.hgmd.cf.ac.uk/), a representative mutation database for genetic diseases, . In addition, even if not listed as a mutation, due to the nature of the mutation, premature truncation of the protein such as frame shift, nonsense, splicing, and initiation codon was caused and the mutation likely mutation was not deleted. We selected only base mutations satisfying a more stringent filtering strategy such as allele depth (≥10) and allele ratio (0.4-0.6 for heterozygote) among the base mutations and tried to reduce the base mutation error due to sequencing error. Finally, 2015 ACMG / AMP guidelines were applied to interpret and classify the meaning of the base mutation. In this way, the first female exon sequence data were analyzed, and one base mutation (SLC26A4), which is the causative gene of autosomal recessive inherited deafness and Pendred syndrome on chromosome 7 (NM_000441.1 standard sequence (C.918-2A> G) was found, and a mutation in the nucleotide sequence found in the SLC26A4 gene of the male exome sequence data was analyzed. And mutation information was reported as shown in Table 1 below. Subsequently, while continuing to analyze female exomnia data, one disease-specific mutation (NM_000053.3 standard sequence c.2333G> T) was found in ATP7B, the causative gene of Wilson's disease on chromosome 13. We analyzed the nucleotide sequence variation found in ATP7B gene in male exocytic sequence data, but no mutation of the disease was found, and the ATP7B gene mutation information found in female was deleted. Since then, the analysis of exon sequence data for women has continued, but no mutation information except for the base mutations found in the SLC26A4 gene has been deleted because there were no additional pathogenic base mutations found.

In the second and third women, mutations in the gene sequence related to autosomal recessive genetic diseases were not found. Thus, only the SLC26A4 mutation found in the first couple was validated by Sanger sequencing method.

Subject Gene cDNA Transcript Protein MIM-phenotype Category Female SLC26A4 NM_000441.1 c.2168A> G p. His723Arg Deafness, autosomal  recessive 4, with enlarged vestibular aqueduct
Pendred  syndrome P Male SLC26A4 NM_000441.1 c.918-2A> G NA Deafness, autosomal  recessive 4, with enlarged vestibular aqueduct
Pendred  syndrome P

* P, pathogenic; LP, likely pathogenic; NA, not available.

1.3. Calculate the risk of future childhood illness

The first couple who showed the possibility of developing an autosomal recessive genetic disease in Example 1.2 calculated the risk of the child's onset. The autosomal recessive genetic diseases of the future children and the mutation information of the causative genes are reported in both male and female heterozygotes, so that they can deliver mutated genetic traits to their children at a probability of 50%. Thus, the risk of developing an autosomal recessive genetic disease in the future of the male and female was finally calculated to be 25%, and was explained through the genetic counseling process to the first couple through a professor in the genetic clinic.

Example 2. Estimation of risk of genetic disease of sex chromosomal recessive child of future child

2.1. Obtain nucleotide sequence data from prospective parents

From two pairs of couples who agreed to examine the possibility of developing sex chromosomal recessive hereditary diseases among the three pairs of married couples visited in Example 1 in order to predict the possibility of genetic diseases of future children, And after obtaining consent, blood samples were taken to obtain exon sequence data. The method for obtaining the exon nucleotide sequence data is the same as in Example 1.1 above.

2.2. Detection and analysis of mutations related to sex chromosomal recessive genetic diseases

Upon receipt of the obtained nucleotide sequence data, the possibility of the occurrence of sex chromosomal recessive diseases of future children was analyzed according to an aspect of the present invention, and exon sequence data of the female was selected as a subject to extract the mutation information. The method for detecting and analyzing mutations from exon nucleotide sequence data is the same as in Example 1.2 above.

In analyzing the second female exome sequence data, one base mutation (NM_000052.6 standard sequence c.2055_2058del) was found in ATP7A, which is the causative gene of Menkes disease on the X chromosome, and the final mutation Information was reported. Since then, the analysis of exon sequence data for women has continued, but no mutation information except the base mutation found in the ATP7A gene has been deleted since there was no additional pathogenic base mutation found.

In the third female, mutation of gene sequence related to sex chromosomal recessive genetic disease was not found. Therefore, according to the above results, only the ATP7A gene mutation found in the female of the second couple was finally validated by the Sanger sequencing method.

Subject Gene cDNA Transcript Protein MIM-phenotype Category Female ATP7A NM_000052.6 c.2055_2058del p. Asn686 * Menkes  disease P

* P, pathogenic; LP, likely pathogenic; NA, not available.

2.3. Calculate the risk of future childhood illness

In Example 2.2, the risk of developing a child was found in a second couple who showed the possibility of developing a sex chromosomal recessive genetic disorder. Females with sex chromosomal recessive genetic diseases and their mutation genes in future children are heterozygous, so they can deliver a mutated genetic trait to their children with a probability of 50%. Sex chromosomal recessive genetic diseases are female children who have received gene mutation, and disease occurs only in male children. Thus, the risk of developing sex chromosomal recessive genetic diseases in the future children of the above-mentioned men and women was calculated to be 0% in female children, and finally 50% in male children, and a genetic counseling course Lt; / RTI >

Example 3. Calculating the risk of dominant genetic diseases that can be treated or prevented in future children

3.1. Obtain nucleotide sequence data from prospective parents

To predict the likelihood of future genetic diseases of future children, a pair of couples who agreed to examine the likelihood of developing a dominant genetic disease that can be treated or prevented among the three pairs of married couples visited in Example 1, After describing and agreeing on predictive tests, blood samples were taken to obtain exon sequence data. The method for obtaining the exon nucleotide sequence data is the same as in Example 1.1 above.

3.2. Detection and analysis of mutations related to dominant genetic diseases that can be treated or prevented

Upon receipt of the obtained nucleotide sequence data, the possibility of occurrence of dominant genetic diseases capable of treating or preventing future children was analyzed according to an aspect of the present invention. Exogenous nucleotide sequence data of male and female were selected Respectively. The method for detecting and analyzing mutations from exon nucleotide sequence data is the same as in Example 1.2 above.

In the third ex-female exome sequence data, no mutations were found in the dominant genetic disease-related mutations that could be treated or prevented. A third base pair mutation (NM_007294.3 standard sequence c.196C> T) was found in BRCA1, a gene responsible for hereditary breast ovarian cancer located on chromosome 17, while analyzing male exon sequence data The final variation information was reported as shown in Table 3 below. Since then, the analysis of exon sequence data for males continued, but no mutation information was found except for the nucleotide mutations found in the BRCA1 gene, as there were no additional pathogenic nucleotide variations found.

Therefore, according to the above results, only the BRCA1 gene mutation found in the male of the third couple was finally validated by the Sanger sequencing method.

Subject Gene cDNA Transcript Protein MIM-phenotype Category Male BRCA1 NM_007294.3 c.196C> T p.66 * Hereditary Breast and Ovarian Cancer P

* P, pathogenic; LP, likely pathogenic; NA, not available.

3.3. Calculating the risk of the likelihood of developing a dominant genetic disease in future children

The third couple, who showed the likelihood of developing a dominant genetic disease that could be treated or prevented in Example 3.2, calculated the risk of the child's onset. Men with reported treatment or preventable dominant genetic disease and mutation of the causative gene of a future child are heterozygous, so they can deliver a mutated genetic trait with a probability of 50% to their child, and 40 Breast cancer can occur at -80%, ovarian cancer can occur at 11-40%, and men with genetic mutations can have prostate cancer at up to 39%. The incidence of pancreatic cancer is predicted to be 1-7%, which is higher than that of people who do not have genetic mutation. Therefore, it is recommended to conduct periodic screening for early detection of cancer and, if desired, Or surgery, this information was explained through a genetic counseling process to a third couple through a professor in the genetic clinic.

According to one embodiment of the present invention, the method of predicting the risk of developing a genetic disease of a future child does not report the genetic information of a parent not causing genetic diseases. Therefore, Can be predicted.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (29)

A method for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject,
Obtaining genomic sequence analysis data of a male subject and a female subject;
Extracting mutations from the genomic sequence analysis data of each object through mapping with a standard nucleotide sequence;
Confirming whether the extracted mutation is associated with autosomal recessive genetic disease;
If the mutation is associated with an autosomal recessive disorder, determining whether the mutated gene has a mutation associated with an autosomal recessive inherited disorder in both of the subjects; And
A method for predicting the risk of developing a genetic disease of a putative progeny, comprising the step of storing mutation information of each subject for the gene when both of the genes have a mutation associated with autosomal recessive genetic disease. 2. The method according to claim 1, wherein said mutation information is deleted when said mutation is not related to autosomal recessive genetic disease. 2. The method according to claim 1, wherein the mutation information is deleted when the mutation related to the autosomal recessive genetic disease is found in the gene in which both of the mutations are not found. The method according to claim 1, wherein the step of verifying whether the mutation is associated with autosomal recessive genetic disease
Confirming whether the mutation is present in an autosomal recessive disease gene;
If the mutation is in an autosomal recessive disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And
And if the mutation does not correspond to a polymorphism, determining whether the mutation corresponds to a known mutation or etiology. 5. The method according to claim 4, wherein the mutation is a polymorphism that does not exist in an autosomal recessive disease gene, does not cause a disease, or does not correspond to a known mutation and does not correspond to a pathogenicity, A method for predicting the risk of offspring genetic disease. 2. The method of claim 1, further comprising: after the step of storing the mutation information, verifying that the stored mutation information is valid. The method according to claim 1, further comprising displaying total stored variation information. 8. The method of claim 7, displaying the risk of developing a genetic disease associated with the stored variation information. The method according to claim 1, wherein the risk of developing a genetic disease associated with stored mutation information is displayed. A method for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject,
a) obtaining genomic sequence analysis data of male and female subjects;
b) extracting mutations from the genomic sequence analysis data of each subject through mapping with standard sequence;
c) determining whether a mutation found in one of the extracted mutations is associated with autosomal recessive genetic disease;
d) if the mutation found in the subject is associated with an autosomal recessive disorder, determining whether the other subject has a mutation in the gene of interest associated with the autosomal recessive disorder;
e) if the other subject has a mutation in the corresponding gene, determining whether the mutation of the other subject is related to autosomal recessive inherited diseases; And
f) storing the mutation information of each subject for the gene if the mutation of the other subject is related to autosomal recessive genetic disease. The method according to claim 10, wherein the mutation information is deleted when the mutation found in the subject is not related to autosomal recessive genetic disease. The method according to claim 10, wherein the mutation information is deleted when the other object does not have a mutation in the gene of mutation related to the autosomal recessive genetic disease. 11. The method according to claim 10, wherein the mutation information is deleted when the mutation of the other object is not related to autosomal recessive genetic disease. 11. The method of claim 10, wherein determining whether the mutation found in the subject is associated with autosomal recessive genetic disease
Confirming whether the mutation is present in an autosomal recessive disease gene;
If the mutation is in an autosomal recessive disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And
And if the mutation does not correspond to a polymorphism, determining whether the mutation corresponds to a known mutation or etiology. 11. The method of claim 10, wherein the step of verifying that the mutation of the other subject is associated with autosomal recessive genetic disease
Confirming whether said mutation corresponds to a polymorphism that does not cause disease; And
And if the mutation does not correspond to a polymorphism, determining whether the mutation corresponds to a known mutation or etiology. [Claim 15] The method according to claim 15, wherein the mutation of the other subject corresponds to a polymorphism that does not cause disease, or when the mutation does not correspond to a known mutation, How to predict. 11. The method of claim 10, further comprising: after the step of storing the mutation information, verifying that the stored mutation information is valid. 11. The method of claim 10, further comprising displaying total stored variation information. The method according to claim 10, wherein the step c) to step f) are sequentially performed for each mutation by selecting any mutation from the mutation extracted from one subject. [19] The method according to claim 19, wherein, when the mutation of the arbitrarily selected subject is not related to autosomal recessive disorder, the other subject does not have a mutation in the corresponding gene of the mutation associated with the autosomal recessive inherited disorder, If the mutation of another subject is not associated with an autosomal recessive genetic disorder then the mutation information is deleted and the next genetically selected mutation is immediately followed by steps c) through f) How to predict. A method for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject,
Obtaining genomic sequence analysis data of a female subject;
Extracting a mutation from the genome sequence analysis data of the female subject obtained through mapping with a standard nucleotide sequence;
Confirming whether the extracted mutation is associated with a sex chromosomal recessive genetic disorder; And
Storing the mutation information when the mutation is related to a sex chromosomal recessive inheritance disorder and deleting the mutation information when the mutation is not related to the sex chromosomal recessive inheritance disorder; / RTI > 22. The method of claim 21, wherein the step of verifying that the extracted mutation is associated with a sex chromosomal recessive inheritance disorder
Confirming whether the extracted mutation is present in a sex chromosomal recessive disease gene;
If the mutation is in a sex chromosomal recessive disorder disease gene, determining whether the mutation corresponds to a polymorphism that does not cause the disease; And
Determining whether said mutation corresponds to a known mutation or etiology if said mutation does not correspond to a polymorphism that does not cause the disease. 22. The method of claim 21, further comprising verifying that the stored variation information is valid in the female subject. 22. The method of claim 21, further comprising displaying the stored variation information results. A method for predicting the risk of developing a genetic disease of a putative progeny between a male subject and a female subject,
Obtaining genomic sequence analysis data of a male subject and a female subject;
Extracting mutations from the genomic sequence analysis data of each object through mapping with a standard nucleotide sequence;
Determining whether the extracted mutation is associated with a treatable or preventable dominant genetic disease; And
Storing the mutation information if the mutation is related to a dominant genetic disease treatable or preventable and deleting the mutation information if the mutation is not related to a genetic disease treatable or preventable, A method for predicting the risk of disease outbreak. Confirming whether the extracted mutation is associated with a treatable or preventable dominant genetic disease
Confirming whether the extracted mutation is present in a gene for treatment or preventable dominant genetic disease;
Determining whether the mutation is a polymorphism that does not cause the disease if the mutation is present in a therapeutic or preventable dominant genetic disease gene; And
Determining whether the mutation corresponds to a known mutation or etiology if the mutation does not correspond to a polymorphism that does not cause the disease. 26. The method of claim 25, further comprising verifying that the stored variation information is valid in an object having the stored variation information. 26. The method of claim 25, further comprising displaying the stored variation information results. A computer-readable recording medium storing a program for causing a computer to execute the method according to any one of claims 1 to 28.

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