Genome-Wide Linkage Analysis and Association Study Identifies Loci for Polydactyly in Chickens

Abstract

Polydactyly occurs in some chicken breeds, but the molecular mechanism remains incompletely understood. Combined genome-wide linkage analysis and association study (GWAS) for chicken polydactyly helps identify loci or candidate genes for the trait and potentially provides further mechanistic understanding of this phenotype in chickens and perhaps other species. The linkage analysis and GWAS for polydactyly was conducted using an F2 population derived from Beijing-You chickens and commercial broilers. The results identified two QTLs through linkage analysis and seven single-nucleotide polymorphisms (SNPs) through GWAS, associated with the polydactyly trait. One QTL located at 35 cM on the GGA2 was significant at the 1% genome-wise level and another QTL at the 1% chromosome-wide significance level was detected at 39 cM on GGA19. A total of seven SNPs, four of 5% genome-wide significance (P < 2.98 × 10−6) and three of suggestive significance (5.96 × 10−5) were identified, including two SNPs (GGaluGA132178 and Gga_rs14135036) in the QTL on GGA2. Of the identified SNPs, the eight nearest genes were sonic hedgehog (SHH), limb region 1 homolog (mouse) (LMBR1), dipeptidyl-peptidase 6, transcript variant 3 (DPP6), thyroid-stimulating hormone, beta (TSHB), sal-like 4 (Drosophila) (SALL4), par-6 partitioning defective 6 homolog beta (Caenorhabditis elegans) (PARD6B), coenzyme Q5 (COQ5), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, etapolypeptide (YWHAH). The GWAS supports earlier reports of the importance of SHH and LMBR1 as regulating genes for polydactyly in chickens and other species, and identified others, most of which have not previously been associated with limb development. The genes and associated SNPs revealed here provide detailed information for further exploring the molecular and developmental mechanisms underlying polydactyly.

RETRACTED: The identification of loci for polydactyly in chickens using a genome-wide association study

“…Based on the 60 K SNP chip, the previous study identified 7 SNPs associated with the chicken polydactyly (Sun et al, 2014). As mentioned above, we both detected an association signal within the intergenic region between LMBR1 and SHH.…”

“…associated with the chicken polydactyly condition (Dorshorst et al, 2010). The intergenic region is of particular interest because a polymorphism Gga_rs14135036 located here also showed an association with the chicken polydactyly in a previous study (Sun et al, 2014). The SNP rs313965877, located intronic to RNA binding motif protein 33 (RBM33) gene, was identified to be significantly associated with the disorder phenotype (P = 2.39 × 10 −7 ).…”

“…Pitel and Yang mapped the genomic region responsible for the phenotype on the short arm of chromosome 2 in chickens with microsatellite markers (Pitel et al, 2000;Yang et al, 2013). A recent study in chickens also identified seven associated SNPs on chromosomes 2, 15, 20 and 26 (Sun et al, 2014). However, the genes and genetic mechanism underlying this trait remain obscure.…”

DPP6 Domains Responsible for Its Localization and Function

“…Foeger et al (2012) found that heterologously expressed DPP6 localizes to the cell surface in the absence of Kv4.2 in mouse cortex (23) while Nadin and Pfaffinger (34) reported that DPP6 interacts with the K2P channel TASK-3 to regulate resting membrane potential and input resistance in cerebellar granule cells (34). Moreover numerous genome-wide association screens for a variety of maladies implicate a potential role for DPP6 (26,27,35,36). Further studies will be required to determine which DPP6 domains are responsible for its various functions but it seems likely that its role in regulating filopodia involves an interaction between its ␤-propeller structure located in the cysteine-rich domain and the extracellular matrix protein fibronectin (11) as found for DPPIV (10) (37).…”

Genomewide association study of immune traits in chicken F2 resource population

“…,b), polydactyly (Sun et al . ) and physical appearance traits (accept from G3). In the present study, our aim was to identify potential loci and candidate genes affecting immune traits using the F2 resource population.…”