Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients.
Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3176806?pdf=render |
| _version_ | 1818609136354459648 |
|---|---|
| author | Koichi Hagiwara Hiroyuki Morino Jun Shiihara Tomoaki Tanaka Hitoshi Miyazawa Tomoko Suzuki Masakazu Kohda Yasushi Okazaki Kuniaki Seyama Hideshi Kawakami |
| author_facet | Koichi Hagiwara Hiroyuki Morino Jun Shiihara Tomoaki Tanaka Hitoshi Miyazawa Tomoko Suzuki Masakazu Kohda Yasushi Okazaki Kuniaki Seyama Hideshi Kawakami |
| author_sort | Koichi Hagiwara |
| collection | DOAJ |
| description | Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type α1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1.2-21.8 centimorgans, median: 1.6 centimorgans). For a test population in which these 6 patients and 54 healthy subjects were scrambled, the approach accurately identified these 6 patients and pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data revealed that the analysis works well for IBD fragment derived from a most recent common ancestor (MRCA) who existed less than 60 generations ago. The analysis is unsuitable for the genes with a frequency in general population more than 0.1. Thus, HM on HH analysis is a powerful technique, applicable to a small number of patients not known to be related, and will accelerate the identification of disease-causing genes for recessive conditions. |
| first_indexed | 2024-12-16T14:53:44Z |
| format | Article |
| id | doaj.art-30721c9c133d480b9ba089b1f354d12f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T14:53:44Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-30721c9c133d480b9ba089b1f354d12f2022-12-21T22:27:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2505910.1371/journal.pone.0025059Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients.Koichi HagiwaraHiroyuki MorinoJun ShiiharaTomoaki TanakaHitoshi MiyazawaTomoko SuzukiMasakazu KohdaYasushi OkazakiKuniaki SeyamaHideshi KawakamiGenes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type α1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1.2-21.8 centimorgans, median: 1.6 centimorgans). For a test population in which these 6 patients and 54 healthy subjects were scrambled, the approach accurately identified these 6 patients and pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data revealed that the analysis works well for IBD fragment derived from a most recent common ancestor (MRCA) who existed less than 60 generations ago. The analysis is unsuitable for the genes with a frequency in general population more than 0.1. Thus, HM on HH analysis is a powerful technique, applicable to a small number of patients not known to be related, and will accelerate the identification of disease-causing genes for recessive conditions.http://europepmc.org/articles/PMC3176806?pdf=render |
| spellingShingle | Koichi Hagiwara Hiroyuki Morino Jun Shiihara Tomoaki Tanaka Hitoshi Miyazawa Tomoko Suzuki Masakazu Kohda Yasushi Okazaki Kuniaki Seyama Hideshi Kawakami Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. PLoS ONE |
| title | Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| title_full | Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| title_fullStr | Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| title_full_unstemmed | Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| title_short | Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| title_sort | homozygosity mapping on homozygosity haplotype analysis to detect recessive disease causing genes from a small number of unrelated outbred patients |
| url | http://europepmc.org/articles/PMC3176806?pdf=render |
| work_keys_str_mv | AT koichihagiwara homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT hiroyukimorino homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT junshiihara homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT tomoakitanaka homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT hitoshimiyazawa homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT tomokosuzuki homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT masakazukohda homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT yasushiokazaki homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT kuniakiseyama homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients AT hideshikawakami homozygositymappingonhomozygosityhaplotypeanalysistodetectrecessivediseasecausinggenesfromasmallnumberofunrelatedoutbredpatients |