Diverse Genome-Wide Study of IRD Lineages

Article: Genomic Study Revealing Among Diverse Populations with Inherited Retinal Disease
Source: University of California, San Diego, Medicine
Published: October 19, 2021

Summary of findings and population distribution
of novel mutations in the study population

Inherited retinal diseases (IRD) are a diverse group of pathologies resulting from genetic mutations. Examples include retinal dystrophies such as retinitis pigmentosa, Leber congenital amaurosis, choroideremia, and ocular albinism. It is estimated that at least 260 different gene variants contribute to IRD etiologies. Although rare, IRDs affect people of all ages, with few, if any, treatment options. An international team of scientists led by researchers at UCSD are studying how inherited retinal dystrophies affect different populations of people and, in doing so, have also identified new causative gene variants. The researchers conducted whole-genome sequences (WGS) of 409 individuals from 108 unrelated family lineages (pedigrees), each with a previously diagnosed IRD. Genetic analysis, at a minimum of 30X depth, included linkage analysis and exome sequencing, which had not been performed in earlier gene sequencing of these 108 pedigrees. The study participants were recruited from three ethnic and geographic backgrounds, two of which from understudied populations: Mexico, Pakistan, and European American living in the U.S. Genomic analysis from blood samples revealed causative variants in 61 of the 108 pedigrees (57%), with a total of 93 causative variants in those 61 families. Among the 93 causative variants, 39 were newly reported. The authors note that more than half of the new variants were not listed in the Genome Aggregation Database (gnomAD), an international compilation of genomic data. Clinical diagnosis was consistent with 57 of the pedigrees, and 4 of the pedigrees were reclassified by the researchers. The whole-genome sequencing also identified "unexpected" genotypes specific to the study population, including 4 pedigrees carrying more than one IRD gene among all affected family members, one pedigree wherein different family members carried causal variants in different IRD genes, and one de-novo mutation. Taken together, the study revealed a variety of IRD variants and "shed light on the genetic architecture of IRD in these diverse global populations."

My rating of this study: ⭐⭐⭐

Biswas P, Villanueva AL, Soto-Hermida A, et al. "Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis." PLOS Genetics.  18 October 2021. https://doi.org/10.1371/journal.pgen.1009848