Dog colour patterns explained by modular promoters of ancient canid origin

Distinctive colour patterns in dogs are an integral component of canine diversity. Colour pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves but important gaps remain in understanding how these patterns evolved and are genetically controlled. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments. Here, we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog colour patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with Arctic white wolves and that its hair cycle-specific module probably originated from an extinct canid that diverged from grey wolves more than 2 million years ago. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread colour variation in dogs and wolves.

Interactions between Gene Variants within the COL1A1 and COL5A1 Genes and Musculoskeletal Injuries in Physically Active Caucasian

The COL1A1 and COL5A1 variants have been associated with the risk of musculoskeletal injuries. Therefore, the main aim of the study was to investigate the association between three polymorphisms within two genes (rs1800012 in COL1A1, as well as rs12722 and rs13946 in COL5A1) and the reported, yet rarely described in the literature, injuries of the joint and muscle area in a physically active Caucasian population. Polish students (n = 114) were recruited and divided into the following two groups: students with (n = 53) and without (n = 61) injures. Genotyping was carried out using real-time PCR. The results obtained revealed a statistically significant association between rs1800012 COL1A1 and injury under an overdominant model. Specifically, when adjusted for age and sex, the GT heterozygotes had a 2.2 times higher chance of being injured compared with both homozygotes (TT and GG, 95% CI 0.59–5.07, p = 0.040). However, no significant interaction between the COL5A1 variants, either individually or in haplotype combination, and susceptibility to injury were found. In addition, the gene–gene interaction analysis did not reveal important relationships with the musculoskeletal injury status. It was demonstrated that rs1800012 COL1A1 may be positively associated with physical activity-related injuries in a Caucasian population. Harboring the specific GT genotype may be linked to a higher risk of being injured.

Dog color patterns explained by modular promoters of ancient canid origin

Distinctive color patterns in dogs are an integral component of canine diversity. Color pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves 1,2 but important gaps remain in understanding how these patterns evolved and are genetically controlled 3,4. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments 3,5-7. Here we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog color patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with arctic white wolves and that its hair cycle-specific module likely originated from an extinct canid that diverged from grey wolves more than 2 million years before present. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread color variation in dogs and wolves.

Haplotypes of the Mutated SIRT2 Promoter Contributing to Transcription Factor Binding and Type 2 Diabetes Susceptibility

Genetic variability is an important causative factor for susceptibility and pathogenesis of type 2 diabetes (T2D). Histone deacetylase, sirtuin 2 (SIRT2), plays regulatory roles in glucose metabolism and insulin sensitivity. However, whether the SIRT2 variants or haplotypes contribute to T2D risk remain to be elucidated. In this study, we first detected three novel polymorphisms (P-MU1, P-MU2, and P-MU3) in the promoter of SIRT2 in the Chinese population. All pairwise sets of the three loci were strongly in linkage disequilibrium. Next, we constructed the haplotype block structure, and found H1-GGC and H2-CCA accounted for the most (total 91.8%) in T2D. The haplotype combination H1-H1-GGGGCC displayed a high risk for T2D (OR = 2.03, 95% CI = 1.12–3.72). By association analysis, we found the individuals carrying H1-H1-GGGGCC had significantly higher fasting plasma glucose and glycated hemoglobin. The haplotype H1-GGC presented a 6.74-fold higher promoter activity than H2-CCA, which was consistent with the correlation results. Furthermore, we clarified the mechanism whereby the C allele of both the P-MU1 and P-MU2 loci disrupted the signal transducer and activator of transcription 1 (STAT1) binding sites, leading to the attenuation of the SIRT2 transcription. Together, these data suggest that the linked haplotype GGC could be considered as a promising marker for T2D diagnosis and therapy assessment.

Protective Effect of the MCP-1 Gene Haplotype against Schizophrenia

While cytokines and their genetic variants have been intensively studied in schizophrenia, little attention has been focused on chemokines in the last years. The monocyte chemoattractant protein 1 (MCP-1) is known to attract peripheral monocytes to the brain during an inflammatory reaction and to affect the T helper (Th) cell development by stimulating Th2 polarization. Owing to the neuroinflammation in schizophrenia and the variable level of MCP-1 in these patients’ sera, we proposed to analyze the impact of functional genetic variants of the MCP-1 gene (MCP-1-2518A/G (rs1024611), MCP-1-362G/C (rs2857656), and MCP-1 int1del554-567 (rs3917887)) in schizophrenic patients. We conducted a case-control study on a Tunisian population composed of 200 patients and 200 controls using RFLP-PCR. Our results indicated that the minor alleles (-2518G and Del554-567) were significantly more prevalent in controls than in patients (P=0.001/adjusted OR = 0.42, P=0.04/adjusted OR = 0.64), whereas, for -362C minor allele, increased risk of schizophrenia was revealed (P=0.001, adjusted OR = 2.38). In conclusion, we have identified the haplotype combination -2581G/-362G/int1del554-567 that could mediate protection against schizophrenia (P=0.0038, OR = 0.19) and the effect could result more strongly from the MCP-1 -2582G with -362G variants, whereas the effect of int1del554-567 may in part be explained by its LD with -362.

Identification of the Invasive Form of Corbicula Clams in Ireland

The basket clam genus, Corbicula, commonly known as the Asian clam, has become one of the most internationally high-profile and widespread aquatic invasive species. This genus is now considered to comprise a polymorphic species complex. The international invasion of Corbicula is characterised by four lineages, each fixed for one morphotype, genotype and haplotype combination: the American form (A) and European round form (R), the American form (C) and European saddle from (S), American form B, form round light colour (Rlc) and an intermediate between forms R and S known as Int. We investigated the genetic and morphometric makeup of each Irish population in order to establish which invasive lineages were present so as to identify the number of introductions to Ireland. A combination of morphometric, mitochondrial cytochrome oxidase subunit I (mtCOI) gene analysis and microsatellite markers were used to determine the invasive form at each Irish site. All Irish Corbicula samples conformed morphometrically to the invasive form A/R. All mtCOI sequences retrieved for 25 Irish individuals were identical to the international A/R form, while microsatellite markers again showed a common clustering with the international A/R forms of Corbicula. The combined approach of morphometries, total genomic DNA and microsatellite markers indicate only one form of Corbicula invaded Ireland; the international A/R form.

Association between <i>Fbxl5</i> gene polymorphisms and partial economic traits in Jinghai Yellow chickens

The Fbxl5 gene is a member of the F-BOX family and plays an important role in maintaining iron homeostasis in cells. In order to reveal the genetic effects of Fbxl5 gene polymorphisms on body weight (BW) traits and reproductive performance in chickens, Fbxl5 gene polymorphisms were detected in 363 Jinghai Yellow chickens by PCR-single-strand conformation polymorphism (SSCP) and DNA sequencing methods using three primers. With primer 1, three genotypes (BB, bb, Bb) were detected in the Jinghai Yellow chicken population and two mutations (g. 14257 T > C and g. 14262 T > C) were revealed by gene sequencing. With primer 2, two genotypes (EE, Ee) were detected in the same population and one mutation (g. 19018 G > A), and for primer 3, three genotypes (FF, ff, Ff) and one mutation (g. 19018 G > A) were detected. Four single nucleotide polymorphisms (SNPs) were used to estimate the frequency distributions of the eight haplotypes with PHASE 2.1 software. CTCG was the major haplotype with a frequency of 37.93 %, while the least frequent was TCTA with a frequency of 2.98 %. The BW of haplotype combination H1H8 was higher than that of the other haplotypes and was a dominant combination. In terms of reproductive performance, the age at the first egg of the haplotype combination H9H1 was later than in the other haplotypes, but the mean egg weight at 300 days was relatively optimal. The H1H2 haplotype produced the highest mean egg weight in 300 days, although the total number of eggs in 300 days was smaller in the H2H4 haplotype with the highest at first egg. Therefore, we can consider using the haplotype combination H1H2 for selection. The findings of this study expand the theoretical basis of the use of the Fbxl5 gene in the molecular breeding of poultry.