Gene-Trait Similarity Regression for Multimarker-Based Association Analysis

Summary .  We propose a similarity-based regression method to detect associations between traits and multimarker genotypes. The model regresses similarity in traits for pairs of "unrelated" individuals on their haplotype similarities, and detects the significance by a score test for which the limiting distribution is derived. The proposed method allows for covariates, uses phase-independent similarity measures to bypass the needs to impute phase information, and is applicable to traits of general types (e.g., quantitative and qualitative traits). We also show that the gene-trait similarity regression is closely connected with random effects haplotype analysis, although commonly they are considered as separate modeling tools. This connection unites the classic haplotype sharing methods with the variance-component approaches, which enables direct derivation of analytical properties of the sharing statistics even when the similarity regression model becomes analytically challenging.     

An informative set of SSLP markers and genomic profiles in the rat MHC,the <Emphasis Type="Italic">RT1</Emphasis> complex

Almost 10,000 single nucleotide polymorphisms (SNPs) had been identified in the RT1 complex, the major histocompatibility complex of the rat, but less than ∼0.5% have been characterized. In the context of the incomplete characterization of most SNPs, simple sequence length polymorphism (SSLP) marker development is still valuable for understanding the involvement of genes in the RT1 in controlling disease susceptibility, since SSLPs are user-friendly and cost-effective genetic markers in rat genome analysis. In this study, we developed a set of 67 SSLP markers, including 57 novel markers, to cover the entire RT1 complex and then created genetic profiles across 67 rat strains. These markers are located almost every 50 kb in the RT1 complex and show comparable polymorphism; the average number of alleles was 8.04 ± 3.44 and the average polymorphic rate was 71 ± 23%. Interestingly, markers failing to amplify polymerase chain reaction products were highly observed in all strains except for BN/SsNHsd, which suggests the existence of highly variable genomic sequences or genomic rearrangements in the RT1 region across rat strains. Based on the phylogenic tree and individual genotyping data, we identified 28 SSLP marker haplotypes in the RT1 region that roughly consisted of three genomic regions. These findings provided new insight into the genomic organization of the RT1 complex and we recognized the need of additional RT1 genome sequences in different strains. Owing to the accuracy and ease of determination, PCR-based SSLP genotyping could replace serological typing in genetic analyses and characterization of rat major histocompatibility. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Benzimidazole resistance allele haplotype diversity in United Kingdom isolates of Teladorsagia circumcincta supports a hypothesis of multiple origins of resistance by recurrent mutation

Polymorphisms in the isotype I β-tubulin gene are important genetic determinants of benzimidazole (BZ) resistance in a number of parasitic nematode species including Teladorsagia circumcincta, a major gastrointestinal nematode of sheep. This study investigates the genetic diversity at this locus in a BZ-resistant isolate of T. circumcincta (MTci5) derived from a sheep farm in the United Kingdom (UK) that was open to animal, and therefore parasite, migration. Pyrosequencing was used to determine the frequency of single nucleotide polymorphisms (SNPs) known to be associated with BZ resistance. This was followed by a combination of single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing to sample allelic diversity in a 276 bp fragment immediately surrounding the isotype I β-tubulin F200Y mutation. The genetic diversity at this locus was extremely high, with seven different haplotypes found to contain the resistant F200Y polymorphism in this single resistant isolate. Genotyping by SSCP interfaced with pyrosequencing demonstrated that the P200^Y mutation is also present on multiple haplotypes in two other BZ-resistant T. circumcincta isolates from the UK. This contrasts with much lower levels of haplotype diversity in BZ-resistant alleles present in T. circumcincta isolates from French goat farms that are closed to parasite migration. Taken together with our knowledge of T. circumcincta population genetic structure, these results are most consistent with multiple independent origins of resistance and mixing of alleles due to the large amount of livestock movement in the UK.     

Haplotype diversity in the endosperm specific β-amylase gene Bmy1 of cultivated barley (Hordeum vulgare L.)

Five single nucleotide polymorphism (SNP) sites corresponding to substitutions in the protein sequence of the β-amylase gene Bmy1 at amino acid (AA) positions 115, 165, 233, 347 and 430 were genotyped in 493 cultivated barley accessions by Pyrosequencing and a CAPS assay. A total of 6 different haplotypes for the Bmy1 gene were discovered of which 4 haplotypes were identified as previously described alleles Bmy1-Sd1, Bmy1-Sd2L, Bmy1-Sd2H and Bmy1-Sd3, while 2 haplotypes were new. A broad spectrum of haplotypes was found in spring barleys, while the winter barleys were dominated by the newly described haplotype Bmy1-Sd4. Individual haplotype frequencies varied between the geographic regions.Three pairs of SNP loci within the gene showed highly significant (P<0.0001) elevated values of linkage disequilibrium (LD) with r ² > 0.6. In the European and Asian subpopulations different loci were in linkage disequilibrium due to the differences in haplotype frequency distributions. By applying LD data to select haplotype tagging SNPs, three SNP sites corresponding to AA positions 115, 233 and 347 were identified that allowed to discriminate 4 haplotypes and to capture 91.6% of the available diversity by distinguishing 452 out of 493 accessions. In a subset of 2-rowed German spring barley varieties 4 SNPs and 2 haplotypes had a significant association with the malting quality parameter final attenuation limit which is related to the total amylolytic enzymatic activity.     

陇东黄土高原石鸡的分子系统地理结构

本文运用聚合链式反应和直接测序的方法测定陇东黄土高原 8个石鸡 (Alectorischukar)地理种群 78个样本的mtDNA控制区 4 91bp ,建立其分子系统地理结构。 78个样本共发现 2 4个变异位点 ,2 5种单倍型。 8个地理种群共享单倍型C1 ,6个种群共享单倍型C2 ,种群间有一定的基因交流。 8个地理种群的 2 5种单倍型在NJ树中相互混杂 ,没有形成独立的地理结构 ,但聚成两个分支。单倍型网络图显示 2 5种单倍型聚成两个星状的集群 ,分别以单倍型C1和C2为中心。这两个群间的遗传差异显著。陇东黄土高原石鸡的系统地理结构属于“系统发生连续 ,具有部分空间隔离”的地理格局。这种地理格局是更新世冰川、泥石流和人类活动共同作用的结果     

European Y-chromosomal lineages in Polynesians: a contrast to the population structure revealed by mtDNA.

We have used Y-chromosomal polymorphisms to trace paternal lineages in Polynesians by use of samples previously typed for mtDNA variants. A genealogical approach utilizing hierarchical analysis of eight rare-event biallelic polymorphisms, seven microsatellite loci, and internal structural analysis of the hypervariable minisatellite, MSY1, has been used to define three major paternal-lineage clusters in Polynesians. Two of these clusters, both defined by novel MSY1 modular structures and representing 55% of the Polynesians studied, are also found in coastal Papua New Guinea. Reduced Polynesian diversity, relative to that in Melanesians, is illustrated by the presence of several examples of identical MSY1 codes and microsatellite haplotypes within these lineage clusters in Polynesians. The complete lack of Y chromosomes having the M4 base substitution in Polynesians, despite their prevalence (64%) in Melanesians, may also be a result of the multiple bottleneck events during the colonization of this region of the world. The origin of the M4 mutation has been dated by use of two independent methods based on microsatellite-haplotype and minisatellite-code diversity. Because of the wide confidence limits on the mutation rates of these loci, the M4 mutation cannot be conclusively dated relative to the colonization of Polynesia, 3,000 years ago. The other major lineage cluster found in Polynesians, defined by a base substitution at the 92R7 locus, represents 27% of the Polynesians studied and, most probably, originates in Europe. This is the first Y-chromosomal evidence of major European admixture with indigenous Polynesian populations and contrasts sharply with the picture given by mtDNA evidence.     

PCR-RFLP analysis of cpDNA in the genus Abies

 We used PCR-RFLP analysis of the chloroplast DNA of the genus Abies (family Pinaceae), to determine if the method could be employed to detect inter-specific variation in this genus and to study how the variation was distributed in different regions of the genome. Ten different chloroplast DNA regions, consisting of coding and non-coding DNA sequences, were amplified with specific primers in ten different Abies taxa. The amplification products were digested with several restriction enzymes. The results showed that the chloroplast genome is highly variable in most of the investigated taxa and contains multiple variable regions that appear to be distributed throughout the whole genome. Species-diagnostic markers were found for four of the ten investigated species. Unexpectedly, intra-specific variation was also detected in four species. It is likely that further studies, including larger sample sizes and/or more powerful methods for the detection of chloroplast DNA variation, will reveal additional variation for this genus. Received: 2 September 1998 / Accepted: 17 September 1998     

Haplotype diversity and distribution pattern of Oecophylla smaragdina (Fabricius) (Hymenoptera,Formicidae) in Bangladesh based on mitochondrial COI genes

Climatic oscillation often have influenced the present distribution and intraspecific genetic diversity Oecophylla smaragdina through its wide range of geographical distribution. Previous phylogeographic study of Asian weaver ant population denotes the evidence of distribution of Indian types in Indian, Sri Lanka and SE Asian types in South Asian countries including Bangladesh. However, recent phylogenetic analysis reveals the overlapping distribution of the Indian and South East Asian clades of O. smaragdina in Bangladesh. The present study aims to identify the haplotypes and it’s networking in Bangladesh based on extensive materials. Sampling was executed according to zonation of 5 areas, demarcated by 3 main rivers during the years 2013 to 2018. Adult O. smaragadina workers were collected from 71 colonies of 67 localities belonging to 47 districts of Bangladesh. A total of 25 haplotypes were identified in Bangladesh comprises 13 and 12 of Indian and SE Asian types, respectively from 93 sequences of Cytochrome c oxidase subunit I (COI) gene of 639 bp. The geographical distribution of this haplotype reveals that the Indian haplotypes are mostly located at the western part of Bangladesh while SE Asian haplotypes were dominated in the Eastern part of the country. Central part of Bangladesh has overlapped with the mixture of both Indian and SE Asian haplotypes. The results of the haplotype network give the evidence of recent expansion of O. smaragdina population in Bangladesh and clarify the evidence of presence of many missing haplotypes in refugee.