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PubMed2000

Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders.

On the basis of studies with animal models, the gene for the low-affinity receptor for immunoglobulin E (IgE) (FCER2, CD23) has been implicated as a candidate for IgE-mediated allergic diseases and bronchial hyperreactivity, or related traits. Given evidence for genetic complexity in atopic disorders, we sought to study two European subpopulations, Finnish and Catalonian. We studied three phenotypic markers: (1) total serum IgE level; (2) asthma; and (3) specific IgE level for a mixture of the most common aeroallergens in Finland. Altogether, eight polymorphic markers spanning a region of 10 cM around the FCER2 gene on chromosome 19p13 were analyzed in 124 families. The physical order of the markers and the location of the FCER2 gene were confirmed by using radiation hybrids. The allele and haplotype association study showed a suggestive haplotype association (significance of p </= 0.03 based on a permutation test) for a high serum IgE response. In a subset of chromosomes segregating with asthma in families with two or more affected members, a single haplotype was found to be highly enriched (p = 8.3 x 10(-6)). However, sequence polymorphisms, which would verify structural differences in the FCER2 gene, were not detected in the coding region of the receptor. Our results suggest that chromosome 19p13 might harbor a genetic determinant of IgE-related traits. Studies in other population samples are needed to verify this finding.

Adult↗
PubMed2004

Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans.

An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (approximately 62%) and with the southern natives contributing more extensively to the female lineages (approximately 56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications.

Chromosomes, Human, Y↗
PubMed2026

Evolution and domestication-trait associations of ultra-long centromere haplotypes in pepper plants.

Centromeric and pericentromeric regions of most eukaryotic genomes are highly repetitive and strongly recombination-suppressed, confounding efforts to resolve genetic variation, population structure and phenotypic associations. Pepper (Capsicum annuum) centromeres are nearly devoid of satellite repeats, facilitating assembly and population-level comparison of centromeric regions. Here we integrate 9 near-complete genome assemblies, CENH3 ChIP-seq profiles from 26 diverse accessions, and resequencing and phenotypic data from ~400 cultivated and wild accessions to investigate population-level diversity and phenotypic relevance of pepper peri/centromeric regions. Functional centromere positions are largely fixed on 8 of 12 chromosomes, whereas the remaining 4 carry distinct centromeric epialleles shaped mainly by centromere repositioning and pericentromeric inversions. Pepper centromeres are embedded within ultra-long centromere-spanning haplotype (cenhap) blocks, ranging from 29.8 to 112.9&#x2009;Mb and collectively covering 23.96% of the genome; each block contains only 1-4 major haplotypes. Some cenhaps may act as supergene-like units and are strongly associated with fruit traits, probably because recombination-suppressed intervals harbour multiple fruit-related genes, including OFP and F-box genes. F2 segregation assays further reveal transmission distortion of chromosomes carrying alternative cenhaps. Together, these findings highlight peri/centromeric regions as underrecognized reservoirs of agronomically important variation.

Centromere↗
PubMed2000

Origin of YAP+ lineages of the human Y-chromosome.

We screened a total of 841 Y-chromosomes representing 36 human populations of wide geographical distribution for the presence of a Y-specific Alu insert (YAP+ chromosomes). The Alu element was found in 77 cases. We tested 5 biallelic and 8 polyallelic markers in 70 out of the 77 YAP+ chromosomes. We could identify the existence of a hierarchical and chronological structuring of ancestral and derived YAP+ lineages, giving rise to 4 haplogroups, 14 subhaplogroups and 60 haplotypes. Moreover, we propose a monophyletic origin for each one of the YAP+ lineages. Out-of-Africa and out-of-Asia models have been suggested to explain the origin and evolution of ancestral and derived YAP+ elements. We analyze the evidence supporting these two hypotheses, and we conclude that the information available does not allow one to decide between the out-of-Asia or out-of-Africa models.

Africa↗
PubMed1995

Functional analysis of avian class I (BFIV) glycoproteins by epitope tagging and mutagenesis in vitro.

Similarities between the physical structures of avian and mammalian major histocompatibility complex (MHC) class I glycoproteins have been proposed based on comparative alignment of their amino acid sequences. To investigate the physical structure of the chicken class I glycoprotein, we cloned the cDNA representing the BFIV locus of the B21 haplotype. A unique, chimeric class I glycoprotein was constructed by incorporating an epitope tag (FLAG) at the N terminus. Monoclonal antibodies to the FLAG epitope served to monitor cell-surface expression for functional analysis of the BFIV21 class I glycoprotein. The chimeric class I glycoprotein was expressed in target cells using an avian leukosis virus (ALV)-derived retrovirus vector (RCASBP). The presence of the FLAG epitope did not interfere with either alloantibody recognition or cytotoxic T lymphocyte interaction. Functional analysis employing site-directed mutagenesis identified BF amino acid residues forming serologic epitopes as well as residues important in antigen presentation to ALV-induced cytotoxic T lymphocytes. BF residues 78 and 81, corresponding to HLA 79 and 82, form an antibody epitope with a slight effect on ALV antigen presentation, consistent with their predicted orientation based on the HLA-A2 crystal structure. Alignment of the BFIV21 sequence with previously published BFIV sequences revealed polymorphisms at position 34 (HLA 34), a monomorphic residues in HLA and H-2. Residue 34 is located in pocket B and is predicted to contact the main-chain carbon of peptides bound in HLA-A2. A site-directed substitution in BFIV residue 34 dramatically alters ALV antigen presentation by the BFIV21 class I glycoprotein. These data indicate that the physical molecular structure of the chicken MHC class I glycoprotein is similar to HLA.

Amino Acid Sequence↗
PubMed2006

Similarity of the allele frequency and linkage disequilibrium pattern of single nucleotide polymorphisms in drug-related gene loci between Thai and northern East Asian populations: implications for tagging SNP selection in Thais.

The similarity of the marker allele frequency and linkage disequilibrium structure between two populations are major factors for the determination of the transferability and efficiency of haplotype tagging SNP derived from one population to use for an indirect association study in another population. To prove the similarity between northern East Asian populations in Hapmap and Thais, 861 SNP in 166 drug-related genes shared between Thais, Han Chinese and Japanese were analyzed for their correlation statistics. Allele frequency, Fst statistics and linkage disequilibrium statistics (r (2)) showed a high correlation between these populations. TagSNP sets derived by an aggressive tagging algorithm from these 861 SNP in Japanese and Chinese were used to test the coverage of East Asia-derived tagSNP in Thais. TagSNP derived from Japanese and Chinese are comparable in the percentage of coverage of the alleles captured with tagSNP at r (2)>or=0.8 (93% vs. 93%) in these drug-related gene loci. Additional tagSNP sets derived from the combination of Japanese- and Chinese-derived tagging SNP sets were used to test the coverage in Thais. The later set improved the percentage of coverage of alleles captured with tagSNP at r (2)>or=0.8-98% for these sites. High similarity between Thais and northern East Asian allele frequency and linkage disequilibrium statistics supported that tagSNPs derived from the northern East Asian population should be useful for an indirect association study in Thais. The combination of non-overlapping Japanese derived tagSNP and Chinese-derived tagSNP improved the percentage of genomic coverage in Thais, at least in these drug-related gene loci.

Algorithms↗
PubMed1999

Population structure of the wood decay fungus Fomitopsis pinicola.

Three populations of the wood decay fungus Fomitopsis pinicola, one from each of three countries (Sweden, Russia and Lithuania), were studied by means of arbitrary primed PCR. The genetic structure of the populations was assessed by inferring the genotype of the genets by studying the haplotypes of several single-spore isolates from one sporocarp for each individual. Heterozygotes could therefore be detected with a dominant genetic marker. The amplified band and the null allele of all loci segregated in a way that was in agreement with a 50:50 ratio. Genetic analysis showed that the total population as well as the subpopulations had heterozygote frequencies in agreement with Hardy-Weinberg expectations. No population differentiation was detected in spite of large geographical distances among the populations studied. We also compared the methods of somatic incompatibility and AP-PCR in terms of their value in detecting fungal genets. This was tested for a sample of dikaryotic mycelia from Switzerland. For the tested material the two methods gave congruent results.

Base Sequence↗
PubMed2006

Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia.

The neuregulin 1 (NRG1) receptor, ErbB4, has been identified as a potential risk gene for schizophrenia. HER4/ErbB4 is a receptor tyrosine kinase whose transcript undergoes alternative splicing in the brain. Exon 16 encodes isoforms containing a metalloprotease cleavable extracellular domain (JM-a), exon 15 for a cleavage resistant form (JM-b) and exon 26 for a cytoplasmic domain (CYT-1) with a phosphotidylinositol-3 kinase (PI3K) binding site. Disease-associated variants in the ErbB4 gene are intronic and implicate altered splicing of the gene. We examined ErbB4 splice-variant gene expression in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in schizophrenia using qPCR and investigated whether expression levels are associated with previously reported genomic risk variants in ErbB4 in a large cohort of human brains. In the DLPFC, we confirmed previous observations, in a separate cohort, that mRNA for ErbB4 splice isoforms containing exon 16 (JM-a) and exon 26 (CYT-1) are significantly elevated in patients with schizophrenia. A main effect of genotype was observed in the DLPFC and hippocampus at a single risk SNP located in intron 12 (rs4673628) on isoforms containing exon 16 (JM-a). We also found that three intronic risk SNPs (rs7598440, rs707284, rs839523) and a core-risk haplotype surrounding exon 3 are strongly associated with elevated expression of splice variants containing exon 26 (CYT-1). These findings suggest that dysregulation of splice-variant specific expression of ErbB4 in the brain underlies the genetic association of the gene with schizophrenia and that the NRG1/ErbB4 signaling pathway may be an important genetic network involved in the pathogenesis of the disease.

Alternative Splicing↗
PubMedDate not supplied

Patterns of genetic structure among populations of an oligophagous pollinating yucca moth (Tegeticula yuccasella).

Plant-insect associations have served as models for investigations of coevolution and the influence of biotic interactions on diversification. The pollination association between yuccas and yucca moths is a classic example of an obligate mutualism often suggested to have been affected by coevolution. Recent work has shown high host specificity in pollinating yucca moths, and here we use Tegeticula yuccasella, the species with the widest diet breadth, to ask how host specificity and isolation by distance contribute to specialization. Isolation by distance at a regional scale was observed in nucleotide variation within the mitochondrial gene cytochrome oxidase I (COI) (r =.294; P =.003). Host-related genetic structure (F(ct) = 0.08) was found to be slightly lower than the level of structure observed between eastern and western moth populations (F(ct) = 0.096). However, 56% of the COI haplotypes sampled from moths on Yucca filamentosa mapped to a host-specific clade in the haplotype network. Taken together, these results suggest that differentiation among T. yuccasella populations on alternative hosts is slight, but gene flow is influenced by both host association and geographic distance.

Animals↗
PubMed2006

Six amino acid substitutions in the carboxyl-transferase domain of the plastidic acetyl-CoA carboxylase gene are linked with resistance to herbicides in a Lolium rigidum population.

The molecular basis of an acetyl-CoA carboxylase (ACCase) target-based resistant Lolium rigidum population (WLR 96) was studied here. The carboxyl-transferase domain of the plastidic ACCase gene from resistant individuals was amplified by PCR and sequenced. The DNA sequences were aligned and compared with a susceptible population. Six amino acid substitutions were identified in the resistant population. The substitution Ile-2041-Asn, known to confer resistance to ACCase-inhibiting herbicides aryloxyphenoxypropionate (APP) in Alopecurus myosuroides, was identified in most resistant plants but it is always linked with other amino acid substitutions. This was confirmed by a cleaved amplified polymorphism (CAP) marker and an allele-specific PCR. The sole amino acid substitution Ile-2041-Asn was not found in this population. It is likely this mutation evolved later among individuals already possessing the other substitutions. Three haplotypes were identified from the resistant population based on the six amino acid combinations, and two are linked with herbicide resistance in this population. The multiple amino acid substitutions including the Ile-2041-Asn form the molecular basis endowing a high degree of resistance to ACCase-inhibiting herbicides in this L. rigidum population.

Acetyl-CoA Carboxylase↗
PubMed2006

[Y-SNP analysis of Bouyei, Gelao, Mulao, Maonan, and Zhuang populations in Guizhou].

To understand the patrilineal genetic structure of Baiyue ethnic group in Guizhou province, we studied the frequencies of Y-chromosome haplotypes which consisted of 10 single nucleotide polymorphisms (SNPs) by using the PCR-RFLP method. Five haplotypes were found in Baiyue ethnic group in Guizhou, among which H8 was the most common, whereas that of Miao in Guizhou tended to be H8, H11 and H12 haplotypes. Compared with Miao in Guizhou, the Guizhou Baiyue (excluding Sui and Dong) was significantly different and could be regarded as an independent ethnic group. Differences were also found in the same ethnic group among different areas.

Asian People↗
PubMed2004

Deletion of a disease resistance nucleotide-binding-site leucine-rich- repeat-like sequence is associated with the loss of the Phytophthora resistance gene Rps4 in soybean.

Resistance of soybean against the oomycete pathogen Phytophthora sojae is conferred by a series of Rps genes. We have characterized a disease resistance gene-like sequence NBSRps4/6 that was introgressed into soybean lines along with Rps4 or Rps6. High-resolution genetic mapping established that NBSRps4/6 cosegregates with Rps4. Two mutants, M1 and M2, showing rearrangements in the NBSRps4/6 region were identified from analyses of 82 F(1)'s and 201 selfed HARO4272 plants containing Rps4. Fingerprints of these mutants are identical to those of HARO4272 for 176 SSR markers representing the whole genome except the NBSRps4/6 region. Both mutants showed a gain of race specificities, distinct from the one encoded by Rps4. To investigate the possible mechanism of gain of Phytophthora resistance in M1, the novel race specificity was mapped. Surprisingly, the gene encoding this resistance mapped to the Rps3 region, indicating that this gene could be either allelic or linked to Rps3. Recombinant analyses have shown that deletion of NBSRps4/6 in M1 is associated with the loss of Rps4 function. The NBSRps4/6 sequence is highly transcribed in etiolated hypocotyls expressing the Phytophthora resistance. It is most likely that a copy of the NBSRps4/6 sequence is the Rps4 gene. Possible mechanisms of the deletion in the NBSRps4/6 region and introgression of two unlinked Rps genes into Harosoy are discussed.

Haplotypes↗
PubMed1976

Evidence for "deleted" or "silent" genes homozygous at the locus coding for the constant region of the gamma3 chain.

Three uncommon stable Gm haplotypes, Gm3;23;--, Gm1,2,17;..;-- and Gm1,17;..;-- have been transmitted through 3 generations of two related Lebanese and Syrian families. No pathological consequence was noted in seven individuals, aged 14--65, whose sera were deficient for all the allotypes carried by the IgG3 chains. Among the different genetic events which could have produced these haplotypes (alteration of a regulatory gene, point mutation, gene hybridization, gene deletion), it appears that a structural deletion is the most probable explanation. The observed data can be explained by either a partial or a total deletion of the constant portion of the IgG3 heavy chain.

Adolescent↗
PubMed2002

Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family.

The killer cell immunoglobulin-like receptors (KIR) form a family of highly homologous immune receptors that regulate the response of natural killer (NK) cells and some T cells. The genetics of the human KIR family is reviewed in this article. In human populations, diversity in KIR genotype arises from variations in gene content and allelic polymorphism. Comparisons of 81 human KIR sequences reveal past events ofgene duplication and recombination, and indicate that individual KIR genes have diversified from the influence of natural selection. Comparison and compilation of population studies reveal extensive KIR genotype variability within human populations and among them. Genomic analysis shows the KIR genes to be close to each other and separated by homologous sequences that promote haplotype diversification through assymetric recombination. In contrast, homologous recombination appears favored at a unique sequence in the center of the KIR locus, and much haplotypic diversity can be explained by recombination between a limited number of gene-content motifs in the centromeric and telomeric halves of the locus. The importance of NK cells for early defenses against infection suggests that human KIR genotype diversity is the accumulated consequence of a history of numerous and successive selective episodes by different pathogens on human NK-cell responses.

Evolution, Molecular↗
PubMed1978

Structural studies on the murine IA alloantigens. II. Molecular weight characterization of the products of the I-A and I-E/C subregions.

Murine splenocytes were radiolabeled with 3H- and 14C-amino acids; the Ia alloantigens encoded by the I-A and I-E/C subregions were isolated by immunoprecipitation and analyzed for structural variation by polyacrylamide gel electrophoresis. The I-A subregion products (k, d, and b haplotypes) are composed of two polypeptides, alpha and beta, with m.w. of 34,000 and 26,000 daltons, respectively. Haplotype-associated differences in m.w. were detected in the I-E/C products of the k, r, p, and d haplotypes. The alpha and beta chains of E/Ck and E/Cr are 34,000 and 28,000 daltons, respectively; E/Cp and E/Cd molecules are composed of 31,000 and 29,000 dalton polypeptides. Thus, there is both subregion (I-A vs I-E/C) and haplotype (E/Ck, E/Cr vs E/Cd, E/Cp) associated variation in the m.w. of the Ia alloantigens. Additionally, the covalent vs noncovalent association of the Ia subunits was examined and it was found that the alpha and beta chains of both I-A and I-E/C are not covalently associated. However, the I-A alpha and beta chains tend to associate through disulfide bonds during detergent lysis; the presence of alkylating agents during cell lysis prevents this association, and only free alpha and beta chains are observed under nonreducing conditions.

Animals↗