Unknown,Transcriptomics,Genomics,Proteomics

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SNP array dataset for genome-wide association study of causal mutations of thyroid follicular cell carcinoma in dogs

ABSTRACT: Familial thyroid cancer originating from follicular cells accounts for 5-15% of all the thyroid carcinoma cases in humans. Previously, we described thyroid follicular cell carcinomas in a large number of the Dutch German longhaired pointers (GLPs) with likely an autosomal recessive inheritance pattern. Here, we investigated the genetic causes of the disease using a combined approach of genome-wide association study, selective sweep analysis, and ROH analysis based on 170k SNP array genotype data. A region 0-5 Mb on chromosome 17 harboring the TPO gene was identified to be associated with the disease.

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Yun Yu

PROVIDER: E-MTAB-10241 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The Lundehund is an old dog breed with remarkable anatomical features including polydactyly in all four limbs and extraordinary flexibility of the spine. We genotyped 28 Lundehund using the canine Illumina high density beadchip to estimate the effective population size (Ne) and inbreeding coefficients as well as to identify potential regions of positive selection. The decay of linkage disequilibrium was slow with r2=0.95 in 50 kb distance. The last 7-200 generations ago, Ne was at 10-13. An increase of Ne was noted in the very recent generations with a peak value of 19 for Ne at generation 4. The FROH estimated for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most likely estimates for FROH after removing identical-by-state segments due to linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has been accumulated through continued inbreeding over 200 generations within a probably closed population with a small effective population size. The mean inbreeding coefficient based on pedigree data for the last 11 generations (FPed=0.10) was strongly biased downwards due to the unknown coancestry of the founders in this pedigree data. The long-range haplotype test identified regions with genes involved in processes of immunity, olfaction, woundhealing and neuronal development as potential targets of selection. The genes QSOX2, BMPR1B and PRRX2 as well as MYOM1 are candidates for selection on the Lundehund characteristics small body size, increased number of digits per paw and extraordinary mobility, respectively. The objectives of the present study were to genotype 28 Lundehund using the canine Illumina high density beadchip (Illumina, San Diego, CA, USA) to estimate the effective population size (Ne) from data on linkage disequilibria (LD). We identified runs of homozygosity (ROH) as regions with a local loss of genetic variation. Inbreeding coefficients were calculated on the basis of pedigree data (FPed) and genotype information (FROH, FIS) to compare the results of these different methods for this population. We applied the long-range haplotype test to search for potential selective sweeps.

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SNP array dataset for genome-wide association study of causal mutations of thyroid follicular cell carcinoma in dogs

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