Natural history of the major histocompatibility complex

Genetic linkage maps are indispensable tools in genetic and genomic studies. Recent development of genotyping-by-sequencing (GBS) methods holds great promise for constructing high-resolution linkage maps in organisms lacking extensive genomic resources. In the present study, linkage mapping was conducted for a bivalve mollusc (Chlamys farreri) using a newly developed GBS method—2b-restriction site-associated DNA (2b-RAD). Genome survey sequencing was performed to generate a preliminary reference genome that was utilized to facilitate linkage and quantitative trait locus (QTL) mapping in C. farreri. A high-resolution linkage map was constructed with a marker density (3806) that has, to our knowledge, never been achieved in any other molluscs. The linkage map covered nearly the whole genome (99.5%) with a resolution of 0.41 cM. QTL mapping and association analysis congruously revealed two growth-related QTLs and one potential sex-determination region. An important candidate QTL gene named PROP1, which functions in the regulation of growth hormone production in vertebrates, was identified from the growth-related QTL region detected on the linkage group LG3. We demonstrate that this linkage map can serve as an important platform for improving genome assembly and unifying multiple genomic resources. Our study, therefore, exemplifies how to build up an integrative genomic framework in a non-model organism.

High-Resolution Linkage and Quantitative Trait Locus Mapping Aided by Genome Survey Sequencing: Building Up An Integrative Genomic Framework for a Bivalve Mollusc

Genome-wide association studies (GWAS) provide a powerful approach for identifying quantitative trait loci without prior knowledge of location or function. To identify loci associated with wool production traits, we performed a genome-wide association study on a total of 765 Chinese Merino sheep (JunKen type) genotyped with 50 K single nucleotide polymorphisms (SNPs). In the present study, five wool production traits were examined: fiber diameter, fiber diameter coefficient of variation, fineness dispersion, staple length and crimp. We detected 28 genome-wide significant SNPs for fiber diameter, fiber diameter coefficient of variation, fineness dispersion, and crimp trait in the Chinese Merino sheep. About 43% of the significant SNP markers were located within known or predicted genes, including YWHAZ, KRTCAP3, TSPEAR, PIK3R4, KIF16B, PTPN3, GPRC5A, DDX47, TCF9, TPTE2, EPHA5 and NBEA genes. Our results not only confirm the results of previous reports, but also provide a suite of novel SNP markers and candidate genes associated with wool traits. Our findings will be useful for exploring the genetic control of wool traits in sheep.

/pdf/genome-wide-association-study-for-wool-production-traits-in-2qrcwm73j2.pdf

Genome-wide association study for wool production traits in a Chinese Merino sheep population.

医科免疫学 = Medical immunology

The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS). This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair) traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic causality and potential epistatic relationships.

/pdf/genome-wide-association-studies-identify-candidate-genes-for-4fyi74z12q.pdf

Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat

Cystic echinococcosis (CE), caused by infection with the larval stage of the cestode Echinococcus granulosus , is a chronic zoonosis, to which sheep are highly susceptible. Previously, we found that Kazakh sheep with different MHC haplotypes differed in CE infection. Sheep with haplotype MHCMva Ibc-Sac IIab-Hin 1Iab were resistant to CE infection, while their counterparts without this haplotype were not. MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at the post-transcriptional level and play essential roles in fundamental biological processes such as development and metabolism. To identify microRNA controlling resistance to CE in the early stage of infection, microRNA profiling was conducted in the intestinal tissue of sheep with resistant and non-resistant MHC haplotypes after peroral infection with E. granulosus eggs. A total of 351 known and 186 novel miRNAs were detected in the resistant group, against 353 known and 129 novel miRNAs in the non-resistant group. Among these miRNAs, 83 known miRNAs were significantly differentially expressed, including 75 up-regulated and 8 down-regulated miRNAs. Among these known microRNAs, miR-21-3p, miR-542-5p, miR-671, miR-134-5p, miR-26b, and miR-27a showed a significantly higher expression in CE-resistant sheep compared to the CE-non-resistant library, with the FC > 3. Functional analysis showed that they were NF-kB pathway-responsive miRNAs, which are involved in the inflammation process. The results suggest that these microRNAs may play important roles in the response of intestinal tissue to E. granulosus .

/pdf/microrna-profiling-of-the-intestinal-tissue-of-kazakh-sheep-jzykkt3ryb.pdf

MicroRNA profiling of the intestinal tissue of Kazakh sheep after experimental Echinococcus granulosus infection, using a high-throughput approach

Regarding mutations of PROP1 (Prophet of POU1F1) gene significantly associating with combined pituitary hormone deficiency (CPHD) in human patients and animals, PROP1 gene is a novel important candidate gene for detecting genetic variation and growth, reproduction, metabolism traits selection and breeding. The aim of this study was to detect PROP1 gene mutation of the exon 1–3 and its association with wool traits in 345 Chinese Merino sheep. In this study, on the basis of PCR-SSCP and DNA sequencing methods, ten novel SNPs within the sheep PROP1 gene, namely, AY533708: g.45A > G resulting in Glu15Glu, g.1198A > G, g.1341G > C resulting in Arg63Ser, g.1389G > A resulting in Ala79Ala, g.1402C > T resulting in Leu84Leu, g.1424A > G resulting in Asn91Ser, g.1522C > T, g.1556A > T, g.1574T > C, g.2430C > G were reported. In addition, association analysis showed that three genotypes of P4 fragment were significantly associated with fiber diameter in the analyzed population (P = 0.044). These results strongly suggested that polymorphisms of the PROP1 gene could be a useful molecular marker for sheep breeding and genetics through marker-assisted selection (MAS).

Identification of SNPs within the sheep PROP1 gene and their effects on wool traits.

The present study aimed at detecting the association of ovine major histocompatibility complex class II (Ovar II) DRB1 gene second exon and susceptibility or resistance to hydatidosis in three sheep breeds of Sinkiang. The MHC-DRB1 second exon was amplified by polymerase chain reaction (PCR) from DNA samples of healthy sheep and sheep with hydatidosis. PCR products were characterized by the restriction fragment length polymorphism (RFLP) technique. Five restriction enzymes, MvaI, HaeIII, SacI, SacII, Hin1I, were used, yielding 14 alleles and 31 restriction patterns. Frequencies of patterns MvaIbc, Hin1Iab, SacIIab, HaeIIIde, HaeIIIdf, HaeIIIdd (P < 0.01) in Kazakh sheep, SacIab (P < 0.05) in Duolang sheep, and HaeIIIab, HaeIIIce, HaeIIIde, HaeIIIee (P < 0.01) in Chinese Merino (Sinkiang Junken type) sheep, were significantly higher in healthy sheep compared with infected sheep. These results indicated a strong association between these patterns and hydatidosis resistance. In contrast, the frequencies of MvaIbb, SacIIaa, Hin1Ibb, HaeIIIef (P < 0.01) and HaeIIIab (P < 0.05) in Kazakh sheep, SacIbb, HaeIIIae, Hin1Iab (P < 0.05), HaeIIIaa, HaeIIIbe, HaeIIIef (P < 0.01) in Duolang sheep, SacIIaa (P < 0.05) and HaeIIIbd, Hin1Ibb, HaeIIIcf, HaeIIIef (P < 0.01) in Chinese Merino sheep (Sinkiang Junken type) were significantly lower in healthy sheep compared with infected sheep. This indicated a strong association between these patterns and hydatidosis susceptibility. In addition, sheep with the pattern of HaeIIIef demonstrated a high hydatidosis susceptibility (P < 0.01) in all three breeds, while sheep with the pattern HaeIIIde demonstrated significant hydatidosis resistance (P < 0.01) in Kazakh and Chinese Merino sheep (Sinkiang Junken type). These results suggest that the Ovar-DRB1 gene plays a role in resistance to hydatidosis infection in the three sheep breeds.

/pdf/the-relationship-between-mhc-drb1-gene-second-exon-woaae5z5ib.pdf

The relationship between MHC-DRB1 gene second exon polymorphism and hydatidosis resistance of Chinese merino (Sinkiang Junken type), Kazakh and Duolang sheep

The aim of this study was to evaluate, through the use of microsatellite markers, the current genetic diversity and the relationships of 375 individuals from 8 local sheep breeds reared in typical breeding farms in the northwest of China, and moreover, to offer a contribution towards genetic conservation decisions for the studied breeds. The expected heterozygosities and allelic richness for the 8 breeds varied from 0.474 to 0.623 and from 3.8 to 5.4, respectively. All the populations showed a significant deficit in heterozygosity and a relatively low level of genetic diversity. Furthermore, the high positive F IS value (ranging from 0.255 to 0.556) indicated inbreeding to be one of the main causes for high genetic homogeneity and lack of heterozygosity in all breeds. The clustering analysis performed with the DISPAN package showed that Aletai, Kazak, Bashibai and Bayinbuluke were grouped together, and Hetian, Qira black and Duolang were grouped together, which indicated that the relationship among breeds displayed some degree of consistency with their geographical distribution, production and origin. These findings indicate that improved conservation measures must be undertaken to avoid further losses of genetic diversity and minimize inbreeding represented by these breeds.

Genetic diversity measures of 8 local sheep breeds in northwest of China for genetic resource conservation.

Background
Cystic Echinococcosis(CE), caused by infection with the larval stage of the cestode Echinococcus granulosus (E. granulosus), is a chronic parasitic zoonosis, with highly susceptible infection in sheep. However, the comprehensive molecular mechanisms that underlie the process of E. granulosus infection in the early stage remain largely unknown. The objective of this present study was to gain a cluster of genes expression profiles in the intestine tissue of sheep infected with CE.

/pdf/an-immediate-innate-immune-response-occurred-in-the-early-p5jsp2pq4j.pdf

Wenqiao Hui

Papers

MicroRNA profiling of the intestinal tissue of Kazakh sheep after experimental Echinococcus granulosus infection, using a high-throughput approach

Identification of SNPs within the sheep PROP1 gene and their effects on wool traits.

The relationship between MHC-DRB1 gene second exon polymorphism and hydatidosis resistance of Chinese merino (Sinkiang Junken type), Kazakh and Duolang sheep

Genetic diversity measures of 8 local sheep breeds in northwest of China for genetic resource conservation.

An Immediate Innate Immune Response Occurred In the Early Stage of E. granulosus Eggs Infection in Sheep: Evidence from Microarray Analysis.