Genetic variants associated with congenital urinary tract obstruction in men

The discovery may help scientists better understand what causes a rare disease called the posterior urethral valve (PUV
).

Dr Melanie Chan, lead author of the study, explains: "PUV does not follow the Mendelian model of inheritance, in which both parents contribute to one of two possible alleles for a trait, and scientists have yet to identify a single genetic cause
.

To determine the genetic causes, Chan and his colleagues analyzed the genomes of 132 unrelated men with PUV and 23,727 individuals without PUV who were recruited into the UK's 100,000 Genomes Project
.

The team then localized the variant on 12q24.

Finally, they showed that structural changes in chromosomes, including changes in DNA flip parts or other changes that alter gene expression regulation, are also associated
with PUV.

"Our study identifies for the first time rare and common genetic variants that are closely related to PUV, as well as chromosomal structural variants that can lead to the disease," Dr.

The authors add that the smaller number of individuals included in this genetic analysis reduces their statistical ability to
detect very rare genetic variants associated with PUV.

But senior author Professor Daniel Gale, chair of St Peter's Nephrology at University College London's Department of Nephrology, said the study demonstrated the importance of including people with different genetic backgrounds in genome-wide studies of
rare diseases.

Increasing the diversity of genetic research is scientifically and ethically beneficial by increasing the power of research to discover and validate rare genetic variants and allowing the detection of genetic variants
that disproportionately affect individuals of Asian, African, or other non-European ancestry.

Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves