Person:
Muller, Jean-Francois

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Muller

First Name

Jean-Francois

Name

Muller, Jean-Francois

Filters

20181

Settings

Author's Publications: search.filters.isAuthorOfPublication.82800a2c-bbec-4345-8d6f-2638eadd28d3

Search Results

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Publication
    Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy
    (SpringerNature, 2018-07-05) Kousi, Maria; Söylemez, Onuralp; Ozanturk, Aysegül; Akle, Sebastian; Jungreis, Irwin; Muller, Jean-Francois; Cassa, Christopher; Brand, Harrison; Mokry, Jill Anne; Wolf, Maxim; Sadeghpour, Azita; McFadden, Kelsey; Lewis, Richard A.; Talkowski, Michael; Dollfus, Hélène; Kellis, Manolis; Davis, Erica E.; Sunyaev, Shamil; Katsanis, Nicholas
    The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remains unclear. We performed a systematic secondary-variant burden analysis of two independent Bardet-Biedl syndrome (BBS)1 cohorts 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 compared to either population controls or to 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 paradigm for secondary-variant burden analysis in recessive disorders.