小柯机器人

美国杜克大学医学中心Nicholas Katsanis研究组揭示隐性纤毛病中生物模块的次生遗传负担和非随机分布。这一研究成果于2020年10月12日在线发表在国际学术期刊《自然—遗传学》上。

Title: Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy

Author: Maria Kousi, Onuralp Sylemez, Aysegl Ozanturk, Niki Mourtzi, Sebastian Akle, Irwin Jungreis, Jean Muller, Christopher A. Cassa, Harrison Brand, Jill Anne Mokry, Maxim Y. Wolf, Azita Sadeghpour, Kelsey McFadden, Richard A. Lewis, Michael E. Talkowski, Hlne Dollfus, Manolis Kellis, Erica E. Davis, Shamil R. Sunyaev, Nicholas Katsanis

Issue&Volume: 2020-10-12

Abstract: The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remain unclear. We performed a systematic secondary-variant burden analysis of two independent cohorts of patients with Bardet–Biedl syndrome (BBS) with known recessive biallelic pathogenic mutations in one of 17 BBS genes for each individual. We observed a significant enrichment of trans-acting rare nonsynonymous secondary variants in patients with BBS compared with either population controls or a cohort of individuals with a non-BBS diagnosis and recessive variants in the same gene set. Strikingly, we found a significant over-representation of secondary alleles in chaperonin-encoding genes—a finding corroborated by the observation of epistatic interactions involving this complex in vivo. These data indicate a complex genetic architecture for BBS that informs the biological properties of disease modules and presents a model for secondary-variant burden analysis in recessive disorders.

DOI: 10.1038/s41588-020-0707-1

Source: https://www.nature.com/articles/s41588-020-0707-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex