title: A quantitatively-modeled homozygosity mapping algorithm, qHomozygosityMapping, utilizing whole genome single nucleotide polymorphism genotyping data.
abstract: Homozygosity mapping is a powerful procedure that is capable of detecting recessive disease-causing genes in a few patients from families with a history of inbreeding. We report here a homozygosity mapping algorithm for high-density single nucleotide polymorphism arrays that is able to (i) correct genotyping errors, (ii) search for autozygous segments genome-wide through regions with runs of homozygous SNPs, (iii) check the validity of the inbreeding history, and (iv) calculate the probability of the disease-causing gene being located in the regions identified. The genotyping error correction restored an average of 94.2% of the total length of all regions with run of homozygous SNPs, and 99.9% of the total length of them that were longer than 2 cM. At the end of the analysis, we would know the probability that regions identified contain a disease-causing gene, and we would be able to determine how much effort should be devoted to scrutinizing the regions. We confirmed the power of this algorithm using 6 patients with Siiyama-type α1-antitrypsin deficiency, a rare autosomal recessive disease in Japan. Our procedure will accelerate the identification of disease-causing genes using high-density SNP array data.
authors.affiliation: Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Saitama 350-0495, Japan.
authors.lastname: Huqun
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohda
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
mesh_terms: D000465:Algorithms; D003241:Consanguinity; D005808:Genes, Recessive / Q000235:genetics; D016678:Genome / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007564:Japan; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics