2026-04-29T04:52:26Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/155682025-05-05T11:06:09Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Matalonga, Leslie author Laurie, Steven author Papakonstantinou, Anastasios author Piscia, Davide author Mereu, Elisabetta author Bullich, Gemma author Thompson, Rachel author Horvath, Rita author Pérez-Jurado, Luis Alberto author Riess, Olaf author Gut, Ivo author van Ommen, Gert-Jan author Lochmüller, Hanns author Beltran, Sergi author RD–Connect Genome-Phenome Analysis Platform author URD-Cat Data Contributors author Posada De la Paz, Manuel author 2020-09 Autozygosity is associated with an increased risk of genetic rare disease, thus being a relevant factor for clinical genetic studies. More than 2400 exome sequencing data sets were analyzed and screened for autozygosity on the basis of detection of >1 Mbp runs of homozygosity (ROHs). A model was built to predict if an individual is likely to be a consanguineous offspring (accuracy, 98%), and probability of consanguinity ranges were established according to the total ROH size. Application of the model resulted in the reclassification of the consanguinity status of 12% of the patients. The analysis of a subset of 79 consanguineous cases with the Rare Disease (RD)-Connect Genome-Phenome Analysis Platform, combining variant filtering and homozygosity mapping, enabled a 50% reduction in the number of candidate variants and the identification of homozygous pathogenic variants in 41 patients, with an overall diagnostic yield of 52%. The newly defined consanguinity ranges provide, for the first time, specific ROH thresholds to estimate inbreeding within a pedigree on disparate exome sequencing data, enabling confirmation or (re)classification of consanguineous status, hence increasing the efficiency of molecular diagnosis and reporting on secondary consanguinity findings, as recommended by American College of Medical Genetics and Genomics guidelines. J Mol Diagn. 2020 Sep;22(9):1205-1215. http://hdl.handle.net/20.500.12105/15568 32619640 10.1016/j.jmoldx.2020.06.008 1943-7811 The Journal of molecular diagnostics : JMD Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity