Project Title: Deciphering the genetic mechanisms of the individuals with isolated cleft palate by whole genome sequencing

Project No: lzp-2020/2-0374

Period: 1 December 2020 – 31 December 2021

Project costs: 100 389.00 EUR

Principle Investigator: Dr. med. Baiba Lāce

Summary

Human face ontogenesis is a complex mechanism, the impairment leading to congenital anomalies. One of the most common anomalies is cleft lip and/or palate (CLP). The mutations in the single genes, GRHL3, IRF6, MSX1, TBX22 etc. cause syndromic forms of CLP. However, the vast majority of CLP is multifactorial.

To elucidate cause of CLP, association studies were conducted in the cohorts of CLP patient parent trios, resulting in more than twelve CLP susceptibility loci, 20–30 strong candidate genes and several copy number variations (CNVs).

Since 2000, we had collected more than 150 CLP patient parent trios in a biobank associated with Genome Database of Latvian Population and did association studies in collaboration with Baltic countries, Central European populations and Americas. Our results confirmed that variations in TGFA, IRF6, BCL3, BMP4, FGF1, FOXE1, COL2A1, COL11A2 and TIMP2 genes are associated with non-syndromic cleft lip with or without cleft palate.

The aim of the current study is to perform whole genome sequencing in the patients with isolated cleft palate from our biobank. Project length is one year; therefore, we selected a smaller and genetically diverse group—isolated cleft palate individuals. We hypothesize that we will identify undiagnosed monogenic disorders and CNVs. Secondly, we will analyze all known CLP candidate genes and susceptibility loci. Publicly available data of our patients will serve as a platform for the future projects in the identification of multifactorial genetic mechanisms of CLP.

Information published 01.12.2020.