Cryptorchidism and scrotal hernia, both being sex-limited complex defects, are the most common congenital defects observed in humans, dogs and pigs. It is believed that these two defects are controlled by multiple genes as well as affected by environmental factors.

In this thesis, 22 or 14 functional and positional candidate genes, respectively, have been evaluated to identify the possible associations for crytorchidism in Siberian Huskies and scrotal hernia in pigs. In the canine cryptorchidism study, 76 single nucleotide polymorphisms (SNPs) were found and 51 out of 76 were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method or directly sequencing in 156 Siberian Huskies. A Sibling-Transmission Disequilibrium Test (sib-TDT) was first applied to the discordant sib sets (n=38), and then to all 156 dogs including 47 families and 15 individuals. Sib-set analyses showed six SNPs distributed in the collagen type II α 1 ( COL2A1 ) gene were significantly associated with cryptorchidism ( P < 0.05). Using a sib-TDT analysis on all 156 dogs, SNP rs23389020 in COL2A1 was suggestively significant ( P < 0.06), but not significant after permutation tests (n=1000). Neither of the two haplotypes formed by the five SNPs in COL2A1 was significantly associated with cryptorchidism.

In the porcine scrotal hernia study, a total of 1,534 pigs were used including a data set of 692 individuals from 298 pig nuclear families and another data set of 340 unaffected and 502 affected male pigs. The SNPs of all candidate genes were analyzed by using PCR and genotyped by using Sequenom MassArray ^{TMsuper> technology. Statistical analyses were performed on the family-trio and the case-control data, respectively. Two genes involved in collagen metabolism including homeobox A10 ( HOXA10 ) and matrix metalloproteinases 2 ( MMP2 ), and one gene as zinc finger protein, multitype 2 ( ZFPM2 ), which is regarded as a candidate gene with the development of diaphragmatic hernias, were significantly associated with scrotal hernia incidence ( P < 0.01, P < 0.05 and P < 0.05, respectively). Animals with these genotypes have relatively high odds ratio (OR) of developing scrotal hernias, 2.21 (1.58-3.09) and 2.43 (1.73-3.42) for the two HOXA10 SNPs, and 4.3 (2.78-6.64) and 4.45 (2.88-6.88) for the two ZFPM2 SNPs, respectively. Another gene, collagen type II α 1 ( COL2A1 ) was potentially involved in hernia development (0.05 < P < 0.1).}

Based on the statistical results, we suspect COL2A1 may be a potentially associated gene with cryptorchidism in Siberian Huskies. HOXA10 , ZFPM2 , and MMP2 , as well as COL2A1 could possibly have important roles in pig scrotal hernia development. The potential associations found in the COL2A1 gene with both cryptorchidism and scrotal hernia can be explained as both defects might be partially regulated by the same group of genetic loci. Moreover, the significant genetic variants found in pig scrotal hernia are possibly useful for the marker assisted selection to remove scrotal henia from the pig industry. Due to the physiological and genome similarities between dogs and pigs with humans, genes associated or suggestively associated with cryptorchidism and scrotal hernias uncovered in this study may be valuable in understanding the molecular mechanisms underlying these defects in humans. Further association studies for both defects are needed to validate our results.