Bibliographic Details
| Title: |
Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients. |
| Authors: |
Koichi Hagiwara, Hiroyuki Morino, Jun Shiihara, Tomoaki Tanaka, Hitoshi Miyazawa, Tomoko Suzuki, Masakazu Kohda, Yasushi Okazaki, Kuniaki Seyama, Hideshi Kawakami |
| Source: |
PLoS ONE, Vol 6, Iss 9, p e25059 (2011) |
| Publisher Information: |
Public Library of Science (PLoS), 2011. |
| Publication Year: |
2011 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
http://europepmc.org/articles/PMC3176806?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0025059 |
| Access URL: |
https://doaj.org/article/30721c9c133d480b9ba089b1f354d12f |
| Accession Number: |
edsdoj.30721c9c133d480b9ba089b1f354d12f |
| Database: |
Directory of Open Access Journals |
