Data from: Direct-to-consumer DNA testing of 6,000 dogs reveals 98.6-kb duplication associated with blue eyes and heterochromia in Siberian Huskies

Consumer genomics enables genetic discovery on an unprecedented scale by
linking very large databases of personal genomic data with phenotype
information voluntarily submitted via web-based surveys. These databases
are having a transformative effect on human genomics research, yielding
insights on increasingly complex traits, behaviors, and disease by
including many thousands of individuals in genome-wide association studies
(GWAS). The promise of consumer genomic data is not limited to human
research, however. Genomic tools for dogs are readily available, with
hundreds of causal Mendelian variants already characterized, because
selection and breeding have led to dramatic phenotypic diversity underlain
by a simple genetic structure. Here, we report the results of the first
consumer genomics study ever conducted in a non-human model: a GWAS of
blue eyes based on more than 3,000 customer dogs with validation panels
including nearly 3,000 more, the largest canine GWAS to date. We
discovered a novel association with blue eyes on chromosome 18 (P =
1.3x10-68) and used both sequence coverage and microarray probe intensity
data to identify the putative causal variant: a 98.6-kb duplication
directly upstream of the Homeobox gene ALX4, which plays an important role
in mammalian eye development. This duplication is largely restricted to
Siberian Huskies, is strongly associated with the blue-eyed phenotype
(chi-square P = 5.2x10-290), and is highly, but not completely, penetrant.
These results underscore the power of consumer-data-driven discovery in
non-human species, especially dogs, where there is intense owner interest
in the personal genomic information of their pets, a high level of
engagement with web-based surveys, and an underlying genetic architecture
ideal for mapping studies.