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What does whole genome sequencing have to do with blind and bobtailed cats?

Lyons LA, Creighton EK, Alhaddad H, et al. Whole genome sequencing in cats, identifies new models for blindness in AIPL1 and somite segmentation in HES7.  BMC Genomics 2016 Mar 31;17(1):265. (Free text article)

The 99 Lives Cat Genome Sequencing Initiative, headed by Dr. Leslie Lyons at the University of Missouri, is moving right along.  Fast progress has been made possible due to reduced cost and improved efficiency of whole genome sequencing (WGS) methodology in the past few years.   This study represents the first comprehensive WGS effort within this initiative to identify causal mutations in the domestic cat, allowing assessment of the efficiency of the WGS and variant calling process using the current cat reference assembly.

The Persian breed is known to have a heritable progressive retinal atrophy (PRA), similar to Leber’s congenital amaurosis (LCA), the most severe and earliest onset form of visual impairment in humans.  Japanese bobtail breed possesses an innocuous heritable breed-defining traits; namely a bobbed tail, which results from a somite segmentation and vertebral column development variation.  Deep WGS of three cats, including one non-PRA affected bobbed tail parent, one PRA-affected non–bobbed tail parent, and one obligate PRA carrier, bobbed tail offspring was conducted to fill sequence gaps in the targeted GWAS region for PRA in Persian cats.  Of the approximately 18 million variants identified, it was determined that PRA was due to a single stop gain mutation located within a LCA candidate gene, AIPL1.  This stop gain variant knocked out >40% of the protein product.  The bobtail variant was located in the HES7 gene.   The HES7 variant was private to the Japanese bobtail breed and not identified in any normal tailed breeds. (GO)

See also:
Gandolfo B, Alhaddad H. Investigation of inherited disease in cats: genetic and genomic strategies over three decades. J Feline Med Surg. 2015 May;17(5):405-15.