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1.
Tumour Biol ; 41(8): 1010428319869096, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31405342

RESUMO

Variable association of transforming growth factor beta 1 (TGFß1) in breast cancer (BC) pathogenesis was documented, and the contribution of specific TGFB1 polymorphisms to the progression of BC and associated features remains poorly understood. We investigated the contribution of TGFB1 rs1800469, rs1800470, rs1800471, and rs1800472 variants and 4-locus TGFB1 haplotypes on BC susceptibility, and pathological presentation of BC subtypes. Study subjects comprised 430 female BC cases, and 498 cancer-free control women. BC-associated pathological parameters were also evaluated for correlation with TGFB1 variants. Results obtained showed that the minor allele frequency (MAF) of rs1800471 (+74G>C) was higher seen in BC cases than in control subjects, and was associated with increased risk of BC. Significant differences in rs1800471 and rs1800469 (-509C>T) genotype distribution were noted between BC cases and controls, which persisted after controlling for key covariates. TGFB1 rs1800472 was positively, while rs1800470 was negatively associated with triple negativity, while rs1800470 positively correlated with menarche, but negatively with tumor size and molecular type, and rs1800469 correlated positively with menstrual irregularity, distant metastasis, nodal status, and hormonotherapy. Heterogeneity in LD pattern was noted between the tested TGFB1 variants. Four-locus (rs1800472-rs1800471-rs1800470-rs1800469) Haploview analysis identified haplotype TGCT to be negatively associated, and haplotypes CGTT and CCCC to be positively associated with BC. This association of CGTT and CCCC, but not TGCT, with BC remained significant after controlling for key covariates. In conclusion, TGFB1 alleles and specific genotypes, and 4-locus TGFB1 haplotypes influence BC susceptibility, suggesting dual association imparted by specific SNP, consistent with dual role for TGFB1 in BC pathogenesis.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Crescimento Transformador beta1/genética , Alelos , Feminino , Frequência do Gene/genética , Humanos , Pessoa de Meia-Idade , Tunísia
2.
Nat Commun ; 10(1): 2989, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278252

RESUMO

Multiple cotton genomes (diploid and tetraploid) have been assembled. However, genomic variations between cultivars of allotetraploid upland cotton (Gossypium hirsutum L.), the most widely planted cotton species in the world, remain unexplored. Here, we use single-molecule long read and Hi-C sequencing technologies to assemble genomes of the two upland cotton cultivars TM-1 and zhongmiansuo24 (ZM24). Comparisons among TM-1 and ZM24 assemblies and the genomes of the diploid ancestors reveal a large amount of genetic variations. Among them, the top three longest structural variations are located on chromosome A08 of the tetraploid upland cotton, which account for ~30% total length of this chromosome. Haplotype analyses of the mapping population derived from these two cultivars and the germplasm panel show suppressed recombination rates in this region. This study provides additional genomic resources for the community, and the identified genetic variations, especially the reduced meiotic recombination on chromosome A08, will help future breeding.


Assuntos
Ordem dos Genes/genética , Gossypium/genética , Haplótipos/genética , Melhoramento Vegetal , Poliploidia , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Variação Genética , Genoma de Planta/genética , Sequenciamento de Nucleotídeos em Larga Escala
3.
Nat Commun ; 10(1): 2985, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278258

RESUMO

Mosaic genetic variants can have major clinical impact. We systematically analyse trio exome sequence data from 4,293 probands from the DDD Study with severe developmental disorders for pathogenic postzygotic mosaicism (PZM) in the child or a clinically-unaffected parent, and use ultrahigh-depth sequencing to validate candidate mosaic variants. We observe that levels of mosaicism for small genetic variants are usually equivalent in both saliva and blood and ~3% of causative de novo mutations exhibit PZM; this is an important observation, as the sibling recurrence risk is extremely low. We identify parental PZM in 21 trios (0.5% of trios), resulting in a substantially increased sibling recurrence risk in future pregnancies. Together, these forms of mosaicism account for 40 (1%) diagnoses in our cohort. Likely child-PZM mutations occur equally on both parental haplotypes, and the penetrance of detectable mosaic pathogenic variants overall is likely to be less than half that of constitutive variants.


Assuntos
Deficiências do Desenvolvimento/genética , Exoma/genética , Mosaicismo , Sequenciamento Completo do Exoma/métodos , Criança , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico , Feminino , Testes Genéticos/métodos , Variação Genética , Haplótipos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Herança Materna/genética , Pais , Herança Paterna/genética
4.
BMC Plant Biol ; 19(1): 296, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286893

RESUMO

BACKGROUND: Premature senescence of flag leaf severely affects wheat yield and quality. Chlorophyll (Chl) degradation is the most obvious symptom during leaf senescence and catalyzed by a series of enzymes. Pheophytin pheophorbide hydrolase (Pheophytinase, PPH) gene encodes a Chl degradation hydrolase. RESULTS: In this study, the coding, genomic and promoter sequences of wheat TaPPH-A gene were cloned. The corresponding lengths were 1467 bp, 4479 bp and 3666 bp, respectively. Sequence structure analysis showed that TaPPH-A contained five exons and four introns. After the multiple sequences alignment of TaPPH-A genome from 36 accessions in a wheat diversity panel, four SNPs and one 2-bp InDel were observed, which formed two haplotypes, TaPPH-7A-1 and TaPPH-7A-2. Based on the SNP at 1299 bp (A/G), a molecular marker TaPPH-7A-dCAPS was developed to distinguish allelic variation (A/G). Using the molecular markers, 13 SSR, and 116 SNP markers, a linkage map of chromosome 7A were integrated. TaPPH-A was mapped on the chromosome region flanked by Xwmc9 (0.94 cM) and AX-95634545 (1.04 cM) on 7A in a DH population. Association analysis between TaPPH-7A allelic variation and agronomic traits found that TaPPH-7A was associated with TGW in 11 of 12 environments and Chl content at grain-filling stage under drought stress using Population 1 consisted of 323 accessions. The accessions possessed TaPPH-7A-1 (A) had higher TGW and Chl content than those possessed TaPPH-7A-2 (G), thus TaPPH-7A-1 (A) was a favorable allelic variation. By analyzing the frequency of favorable allelic variation TaPPH-7A-1 (A) in Population 2 with 157 landraces and Population 3 with 348 modern cultivars, we found it increased from pre-1950 (0) to 1960s (54.5%), then maintained a relatively stable level about 56% from 1960s to 1990s. CONCLUSION: These results suggested the favorable allelic variation TaPPH-7A-1 (A) should be valuable in enhancing grain yield by improving the source (chlorophyll content) and sink (the developing grain) simultaneously. Furthermore, the newly developed molecular marker TaPPH-7A-dCAPS could be integrated into a breeding kit of screening high TGW wheat for marker-assisted selection.


Assuntos
Haplótipos/genética , Proteínas de Plantas/genética , Triticum/genética , Marcadores Genéticos/genética , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Triticum/metabolismo
5.
BMC Vet Res ; 15(1): 241, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296208

RESUMO

BACKGROUND: A major challenge in modern medicine and animal husbandry is the issue of antimicrobial resistance. One approach to solving this potential medical hazard is the selection of farm animals with less susceptibility to infectious diseases. Recent advances in functional genome analysis and quantitative genetics have opened the horizon to apply genetic marker information for efficiently identifying animals with preferential predisposition regarding health traits. The current study characterizes functional traits with a focus on udder health in dairy heifers. The animals were selected for having inherited alternative paternal haplotypes for a genomic region on Bos taurus chromosome (BTA) 18 genetically associated with divergent susceptibility to longevity and animal health, particularly mastitis. RESULTS: In the first weeks of lactation, the q heifers which had inherited the unfavorable (q) paternal haplotype displayed a significantly higher number of udder quarters with very low somatic cell count (< 10,000 cells / ml) compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. This might result in impaired mammary gland sentinel function towards invading pathogens. Furthermore, across the course of the first lactation, there was indication that q half-sib heifers showed higher somatic cell counts, a surrogate trait for udder health, in whole milkings compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. Moreover, heifers with the haplotype Q had a higher feed intake and higher milk yield compared to those with the q haplotype. Results of this study indicate that differences in milk production and calculated energy balance per se are not the main drivers of the genetically determined differences between the BTA18 Q and q groups of heifers. CONCLUSIONS: The paternally inherited haplotype from a targeted BTA18 genomic region affect somatic cell count in udder quarters during the early postpartum period and might also contribute to further aspects of animal's health and performance traits due to indirect effects on feed intake and metabolism.


Assuntos
Glândulas Mamárias Animais/fisiologia , Herança Paterna , Animais , Bovinos , Mapeamento Cromossômico , Ingestão de Alimentos/genética , Metabolismo Energético/genética , Feminino , Haplótipos/genética , Lactação/genética , Masculino , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/genética , Período Pós-Parto
6.
BMC Evol Biol ; 19(1): 145, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311504

RESUMO

BACKGROUND: China is an important biogeographical zone in which the genetic legacies of the Tertiary and Quaternary periods are abundant, and the contemporary geography environment plays an important role in species distribution. Therefore, many biogeographical studies have focused on the organisms of the region, especially zooplankton, which is essential in the formation of biogeographical principles. Moreover, the generality of endemism also reinforces the need for detailed regional studies of zooplankton. Bosmina, a group of cosmopolitan zooplankton, is difficult to identify by morphology, and no genetic data are available to date to assess this species complex in China. In this study, 48 waterbodies were sampled covering a large geographical and ecological range in China, the goal of this research is to explore the species distribution of Bosmina across China and to reveal the genetic information of this species complex, based on two genetic markers (a mtDNA 16S and a nuclear ITS). The diversity of taxa in the Bosmina across China was investigated using molecular tools for the first time. RESULTS: Two main species were detected in 35 waterbodies: an endemic east Asia B. fatalis, and the B. longirostris that has a Holarctic distribution. B. fatalis had lower genetic polymorphism and population differentiation than B. longirostris. B. fatalis was preponderant in central and eastern China, whereas B. longirostris was dominated in western China. The third lineage (B. hagmanni) was only detected in a reservoir (CJR) of eastern China (Guangdong province). Bosmina had limited distribution on the Tibetan plateau. CONCLUSIONS: This study revealed that the biogeography of Bosmina appear to be affected by historical events (Pleistocene glaciations) and contemporary environment (such as altitude, eutrophication and isolated habitat).


Assuntos
Cladóceros/genética , DNA Intergênico/genética , DNA Mitocondrial/genética , Variação Genética , Animais , Núcleo Celular/genética , China , Ecossistema , Marcadores Genéticos , Geografia , Haplótipos/genética , Funções Verossimilhança , Mitocôndrias/genética , Filogenia , Polimorfismo Genético , Zooplâncton/genética
7.
BMC Evol Biol ; 19(1): 114, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170905

RESUMO

BACKGROUND: The Qinghai-Tibetan Plateau (QTP) is the world's highest and largest plateau, but the role of its uplift in the evolution of species or biotas still remains poorly known. Toad-headed lizards of the reproductively bimodal genus Phrynocephalus are a clade of agamids, with all viviparous species restricted to the QTP and adjacent regions. The eastern part of the range of the viviparous taxa is occupied by three closely related but taxonomically controversial species, P. guinanensis, P. putjatia and P. vlangalii. Here, we combined genetic (mitochondrial ND4 gene and nine microsatellite loci), morphological (11 mensural and 11 meristic variables), and ecological (nine climatic variables) data to explore possible scenarios that may explain the discordance between genetic and morphological patterns, and to test whether morphological divergence is associated with local adaptation. RESULTS: We found weak genetic differentiation but pronounced morphological divergence, especially between P. guinanensis and P. vlangalii. Genetically, the species boundary was not so clear between any species pair. Morphologically, the species boundary was clear between P. guinanensis and P. vlangalii but not between other two species pairs. Body size and scale characters accounted best for morphological divergence between species. Morphological divergence was related to habitat types that differ climatically. CONCLUSIONS: Our study provides evidence for genetic and morphological divergence among the three closely related viviparous species of Phrynocephalus lizards, and supports the idea that natural selection in spatially heterogeneous environments can lead to population divergence even in the presence of gene flow. Our study supports the hypothesis that the evolutionary divergence between viviparous Phrynocephalus species was a consequence of environmental change after the uplift of the QTP.


Assuntos
Variação Genética , Lagartos/anatomia & histologia , Lagartos/genética , Animais , Teorema de Bayes , China , Clima , DNA Mitocondrial/genética , Feminino , Genética Populacional , Geografia , Haplótipos/genética , Masculino , Polimorfismo Genético , Análise de Componente Principal , Especificidade da Espécie
8.
BMC Evol Biol ; 19(1): 115, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170910

RESUMO

BACKGROUND: Many species of social insects have large-scale mating and dispersal flights and their populations are therefore often relatively homogenous. In contrast, dispersal on the wing appears to be uncommon in most species of the ant genus Cardiocondyla, because its males are wingless and the winged queens mate in their natal nests before dispersing on foot. Here we examine the population structure of C. venustula from South Africa. This species is of particular interest for the analysis of life history evolution in Cardiocondyla, as it occupies a phylogenetic position between tropical species with multi-queen (polygynous) colonies and fighting males and a Palearctic clade with single-queen colonies and mutually peaceful males. Males of C. venustula exhibit an intermediate strategy between lethal fighting and complete tolerance - they mostly engage in non-lethal fights and defend small territories inside their natal nests. We investigated how this reproductive behavior influences colony and population structure by analyzing samples on two geographic scales in South Africa: a small 40 × 40m2 plot and a larger area with distances up to 5 km between sampling sites in Rietvlei Nature Reserve near Pretoria. RESULTS: Colonies were found to be facultatively polygynous and queens appear to mate only with a single male. The extraordinarily high inbreeding coefficient suggests regular sib-mating. Budding by workers and young queens is the predominant mode of colony-founding and leads to high population viscosity. In addition, some queens appear to found colonies independently or through adoption into foreign nests. CONCLUSION: While C. venustula resembles tropical Cardiocondyla in queen number and mating frequency, it differs by the absence of winged disperser males. Dispersal by solitary, mated queens on foot or by short flights and their adoption by alien colonies might promote gene flow between colonies and counteract prolonged inbreeding. The abundance of suitable habitat and the high density of nests facilitate the spread of this species by budding and together with the apparent resistance against inbreeding make it a highly successful pioneer species and invader of degraded and man-made habitats.


Assuntos
Formigas/fisiologia , Territorialidade , Alelos , Animais , Formigas/genética , DNA Mitocondrial/genética , Feminino , Haplótipos/genética , Heterozigoto , Masculino , Repetições de Microssatélites/genética , Filogenia , Dinâmica Populacional , Comportamento Sexual Animal , África do Sul
9.
BMC Evol Biol ; 19(1): 118, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185884

RESUMO

BACKGROUND: There is a biogeographic break located at 30°S in the southeast Pacific, in a coastal area of strong environmental discontinuities. Several marine benthic taxa with restricted dispersal have a coincident phylogeographic break at 30°S, indicating that genetic structure is moulded by life history traits that limit gene flow and thereby promote divergence and speciation. In order to evaluate intraspecific divergence at this biogeographic break, we investigated the genetic and morphological variation of the directly developing beach isopod Excirolana hirsuticauda along 1900 km of the southeast Pacific coast, across 30°S. RESULTS: The COI sequences and microsatellite data both identified a strong discontinuity between populations of E. hirsuticauda to the north and south of 30°S, and a second weaker phylogeographic break at approximately 35°S. The three genetic groups were evidenced by different past demographic and genetic diversity signatures, and were also clearly distinguished with microsatellite data clustering. The COI sequences established that the genetic divergence of E. hirsuticauda at 30°S started earlier than divergence at 35°. Additionally, the three groups have different past demographic signatures, with probable demographic expansion occurring earlier in the southern group (south of 35°S), associated with Pleistocene interglacial periods. Interestingly, body length, multivariate morphometric analyses, and the morphology of a fertilization-related morphological character in males, the appendix masculina, reinforced the three genetic groups detected with genetic data. CONCLUSIONS: The degree of divergence of COI sequences, microsatellite data, and morphology was concordant and showed two geographic areas in which divergence was promoted at differing historical periods. Variation in the appendix masculina of males has probably promoted reproductive isolation. This variation together with gene flow restrictions promoted by life history traits, small body size, oceanographic discontinuities and sandy-beach habitat continuity, likely influenced species divergence at 30°S in the southeast Pacific coast. The degree of genetic and morphological differentiation of populations to the north and south of 30°S suggests that E. hirsuticauda harbours intraspecific divergence consistent with reproductive isolation and an advanced stage of speciation. The speciation process within E. hirsuticauda has been shaped by both restrictions to gene flow and a prezygotic reproductive barrier.


Assuntos
Isópodes/anatomia & histologia , Isópodes/genética , Filogeografia , Análise de Variância , Animais , Teorema de Bayes , Tamanho Corporal , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Fluxo Gênico , Loci Gênicos , Variação Genética , Haplótipos/genética , Isópodes/classificação , Repetições de Microssatélites/genética , Filogenia , Análise de Componente Principal
11.
Mol Immunol ; 112: 215-222, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31177058

RESUMO

The Rongshui miniature pig is an important model animal for studying livestock disease prevention and control in China. The highly polymorphic swine leukocyte antigen (SLA) has been the focus of considerable interest because of the strong, reproducible associations between particular SLA haplotypes and infectious diseases. In this study, we identified 42 alleles at eight polymorphic SLA loci (SLA-1, SLA-3, SLA-2, SLA-6, DRA, DRB1, DQA, and DQB1) representing seven class I and six class II haplotypes using reverse transcription-polymerase chain reaction (RT-PCR) sequence-based typing and PCR-sequence specific primers in Rongshui miniature pigs. The official names were designated by the SLA Nomenclature Committee of the International Society for Animal Genetics. Seven class I haplotypes, Hp-5b.0, 86.0, 87.0, 88.0, 89.0, 90.0 and 91.0, and four class II haplotypes, Hp-0.18b, 0.19c, 0.41 and 0.47, had not previously been reported in other pig breeds. We also comprehensively analyzed the molecular genetic characterization and phylogenies of the identified alleles and the SLA haplotype diversity in Rongshui miniature pigs. SLA-1 and SLA-6 genes were under positive selection, while SLA-2 was under neutral selection, and the other five genes were under purifying selection. The highly polymorphic new alleles may be derived by nucleotide mutations, insertions and deletions, and fragment recombination, and alleles segregated based on sequence differences and peptide-binding motifs, rather than on pig breed. SLA haplotype diversity was generated by allele/gene conversion and recombination. These results will be helpful for elucidating the molecular genetic mechanisms influencing differential disease resistance among pigs with different SLA haplotypes.


Assuntos
Haplótipos/genética , Antígenos de Histocompatibilidade Classe I/genética , Porco Miniatura/genética , Alelos , Animais , Cruzamento/métodos , China , Feminino , Antígenos de Histocompatibilidade Classe II/genética , Masculino , Biologia Molecular/métodos , Mutação/genética , Nucleotídeos/genética , Filogenia , Suínos
12.
PLoS Genet ; 15(6): e1008178, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31199784

RESUMO

Type 1 diabetes (T1D) is a chronic multi-factorial disorder characterized by the immune-mediated destruction of insulin-producing pancreatic beta cells. Variations at a large number of genes influence susceptibility to spontaneous autoimmune T1D in non-obese diabetic (NOD) mice, one of the most frequently studied animal models for human disease. The genetic analysis of these mice allowed the identification of many insulin-dependent diabetes (Idd) loci and candidate genes, one of them being Cd101. CD101 is a heavily glycosylated transmembrane molecule which exhibits negative-costimulatory functions and promotes regulatory T (Treg) function. It is abundantly expressed on subsets of lymphoid and myeloid cells, particularly within the gastrointestinal tract. We have recently reported that the genotype-dependent expression of CD101 correlates with a decreased susceptibility to T1D in NOD.B6 Idd10 congenic mice compared to parental NOD controls. Here we show that the knockout of CD101 within the introgressed B6-derived Idd10 region increased T1D frequency to that of the NOD strain. This loss of protection from T1D was paralleled by decreased Gr1-expressing myeloid cells and FoxP3+ Tregs and an enhanced accumulation of CD4-positive over CD8-positive T lymphocytes in pancreatic tissues. As compared to CD101+/+ NOD.B6 Idd10 donors, adoptive T cell transfers from CD101-/- NOD.B6 Idd10 mice increased T1D frequency in lymphopenic NOD scid and NOD.B6 Idd10 scid recipients. Increased T1D frequency correlated with a more rapid expansion of the transferred CD101-/- T cells and a lower proportion of recipient Gr1-expressing myeloid cells in the pancreatic lymph nodes. Fewer of the Gr1+ cells in the recipients receiving CD101-/- T cells expressed CD101 and the cells had lower levels of IL-10 and TGF-ß mRNA. Thus, our results connect the Cd101 haplotype-dependent protection from T1D to an anti-diabetogenic function of CD101-expressing Tregs and Gr1-positive myeloid cells and confirm the identity of Cd101 as Idd10.


Assuntos
Antígenos CD/genética , Antígenos Ly/genética , Diabetes Mellitus Tipo 1/genética , Pâncreas/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Diabetes Mellitus Tipo 1/patologia , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença , Haplótipos/genética , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Células Mieloides/imunologia , Células Mieloides/metabolismo , Pâncreas/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
13.
BMC Biol ; 17(1): 50, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234833

RESUMO

BACKGROUND: Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression. RESULTS: We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting. CONCLUSIONS: Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.


Assuntos
Alelos , Expressão Gênica/genética , Impressão Genômica/genética , Haplótipos/genética , Análise Química do Sangue , Linhagem Celular , Humanos , Análise de Sequência de RNA
14.
BMC Bioinformatics ; 20(Suppl 11): 279, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167638

RESUMO

BACKGROUND: Recent advances in whole-genome sequencing and SNP array technology have led to the generation of a large amount of genotype data. Large volumes of genotype data will require faster and more efficient methods for storing and searching the data. Positional Burrows-Wheeler Transform (PBWT) provides an appropriate data structure for bi-allelic data. With the increasing sample sizes, more multi-allelic sites are expected to be observed. Hence, there is a necessity to handle multi-allelic genotype data. RESULTS: In this paper, we introduce a multi-allelic version of the Positional Burrows-Wheeler Transform (mPBWT) based on the bi-allelic version for compression and searching. The time-complexity for constructing the data structure and searching within a panel containing t-allelic sites increases by a factor of t. CONCLUSION: Considering the small value for the possible alleles t, the time increase for the multi-allelic PBWT will be negligible and comparable to the bi-allelic version of PBWT.


Assuntos
Algoritmos , Alelos , Compressão de Dados , Genes , Haplótipos/genética , Humanos , Fatores de Tempo
15.
BMC Evol Biol ; 19(1): 113, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153378

RESUMO

BACKGROUND: The Taklimakan Desert in China is characterized by unique geological and historical dynamics and endemic flora and fauna, but the influence of historical climate oscillations on the evolutionary history of endemic animals is poorly understood. Lepus yarkandensis is an oases-dependent Near Threatened species that lives in fragmented oasis habitats in the Taklimakan Desert, China. We investigated the geological and climatic impacts on its geographical differentiation, demographic history and influence of Pleistocene glacial-interglacial cycles on the evolutionary history of L. yarkandensis. Further, studied the impact of climatic oscillation based modification on phylogeography, distribution and diversification pattern of Yarkand hare by using Cytb (1140 bp), MGF (592 bp) and SPTBN1 (619 bp) markers. Ecological niche modeling (ENM) revealed the evolutionary history of this species in response to climate change during the Quaternary. Paleodistribution modeling was used to identify putative refugia and estimate their historical distributions. RESULTS: Both historical demographic analyses and climatic niche modeling revealed strong effects of glacial climate changes, suggesting recurrent range contractions and expansions. The EBSP results indicated clear population expansion of L. yarkandensis since the Pleistocene. In the "early Pleistocene", the demographic expansion continued from 0.83 MYA to the last glacial period. The ENM analysis supported a wide distribution of Lepus yarkandensis at high altitudes during the last interglacial (LIG) period. During the last glacial maximum (LGM), the suitable climate was reduced and restricted to the western part of the Taklimakan Desert. CONCLUSIONS: Inland aridification, oasis evolution and river flow played major roles in the population differentiation and demographic history of Yarkand hares. Historically, the large, continuous oases in the Taklimakan Desert contained a viable and unique population of L. yarkandensis. The fragmented desert environment might have caused low gene flow between individuals or groups, thus leading to predominant genetic differentiation. The Pleistocene climatic cycles triggered the diversification and expansion of this species during cold and warm periods, respectively, leading to multiple colonization events within the Taklimakan Desert. These events might be due to the expansion of the Taklimakan Desert during the Middle Pleistocene. Yarkand hare previously occupied vast areas at low and intermediate altitudes in Xinjiang, Gansu, Shanxi, Henan and Shaanxi Provinces in China. The past aridification, climate change-induced oasis modifications, changes in river volumes and flow directions, and human activities all affected the population demography and phylogeography of the Yarkand hare.


Assuntos
Evolução Biológica , Ecossistema , Lebres/classificação , Filogeografia , Animais , Teorema de Bayes , China , DNA Mitocondrial/genética , Variação Genética , Haplótipos/genética , Lebres/genética , Modelos Teóricos , Filogenia , Especificidade da Espécie , Fatores de Tempo
16.
Plant Sci ; 285: 193-199, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203884

RESUMO

Wheat domestication was a milestone in the rise of agrarian societies in the Fertile Crescent. As opposed to the freely dispersing seeds of its tetraploid progenitor wild emmer, the hallmark trait of domesticated wheat is intact, harvestable spikes. During domestication, wheat acquired recessive loss-of-function mutations in the Brittle Rachis 1 genes, both in the A genome (BTR1-A) and B genome (BTR1-B). In this study, we probe the geographical provenances of these mutations via haplotype analyses of a collection of wild and domesticated accessions. Our results show that the precursor of the domesticated haplotype of BTR1-A was detected in 32% of the wild accessions gathered throughout the Levant, from central Israel to central Turkey. In contrast, the precursor of the domesticated haplotype of BTR1-B, which carries a distinct 11 bp deletion in the promoter region, was found in only 10% of the tested wild accessions, all from the Southern Levant. Moreover, we identified of a single wild emmer accession in Southern Levant that carries the progenitor haplotypes for both BTR1-A and BTR1-B genes. These observations suggest that at least part of the emmer domestication process occurred in Southern Levant, contrary to the widely held view that the northern part of the Fertile Crescent was the center of wheat domestication.


Assuntos
Domesticação , Genes de Plantas/genética , Proteínas de Plantas/genética , Triticum/genética , Genes de Plantas/fisiologia , Haplótipos/genética , Mutação , Proteínas de Plantas/fisiologia , Regiões Promotoras Genéticas
17.
Mol Immunol ; 112: 40-50, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078115

RESUMO

The classical HLA class I genes (HLA Ia) were extensively studied because of their implication in clinical fields and anthropology. Less is known about worldwide genetic diversity and linkage disequilibrium for non-classical HLA class I genes (HLA Ib) and HLA pseudogenes. Notably, HLA-H, which is deleted in a fraction of the population, remains scarcely explored. The aims of this study were 1/ to get further insight into HLA-H genetic diversity and into how this variability potentially affects its expression and 2/ to define HLA Ib worldwide allelic diversity and linkage. Exome sequence data from the 1000 Genomes Project were used to define second field HLA-A, -E, -F, -G and -H typing using PolyPheMe software. Allelic and two-loci haplotype frequencies were estimated using Gene[Rate] software both at worldwide and continental levels. Eleven novel HLA-H alleles identified in exome data were validated by NGS performed on 25 genomic DNA samples from the same cohort. Phylogenetic analysis and frequency distribution of HLA-H alleles revealed three clades, each predominantly represented in Admixed American, European and East Asian populations, African populations and South Asian populations. Among these eleven novel alleles, two potentially encode complete transmembrane HLA proteins. We confirm the high LD between HLA-H and -A, and between HLA-H and -G, and show the three genes have distinct worldwide allelic distribution. Conversely, HLA-E and HLA-F both showed little LD, displayed restricted allelic diversity and practically no difference in their distribution across the planet. Our work thus reveals an unexpectedly high HLA-H genetic diversity, with alleles highly represented in Asia possibly encoding a functional HLA protein. Functional implication of these results remains to be explored, both in physiological and pathological contexts.


Assuntos
Variação Genética/genética , Antígenos HLA-DQ/genética , Haplótipos/genética , Proteína da Hemocromatose/genética , Alelos , Ásia , Grupo com Ancestrais do Continente Asiático/genética , Frequência do Gene/genética , Genes MHC Classe I/genética , Humanos , Desequilíbrio de Ligação/genética , Filogenia
18.
BMC Bioinformatics ; 20(1): 265, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31132991

RESUMO

BACKGROUND: In standard high throughput sequencing analysis, genetic variants are not assigned to a homologous chromosome of origin. This process, called haplotype phasing, can reveal information important for understanding the relationship between genetic variants and biological phenotypes. For example, in genes that carry multiple heterozygous missense variants, phasing resolves whether one or both gene copies are altered. Here, we present a novel approach to phasing variants that takes advantage of unique properties of paired tumor:normal sequencing data from cancer studies. RESULTS: VAF phasing uses changes in variant allele frequency (VAF) between tumor and normal samples in regions of somatic chromosomal gain or loss to phase germline variants. We apply VAF phasing to 6180 samples from the Cancer Genome Atlas (TCGA) and demonstrate that our method is highly concordant with other standard phasing methods, and can phase an average of 33% more variants than other read-backed phasing methods. Using variant annotation tools designed to score gene haplotypes, we find a suggestive association between carrying multiple missense variants in a single copy of a cancer predisposition gene and earlier age of cancer diagnosis. CONCLUSIONS: VAF phasing exploits unique properties of tumor genomes to increase the number of germline variants that can be phased over standard read-backed methods in paired tumor:normal samples. Our phase-informed association testing results call attention to the need to develop more tools for assessing the joint effect of multiple genetic variants.


Assuntos
Variação Genética , Neoplasias/genética , Análise de Sequência de DNA , Sequência de Bases , Variações do Número de Cópias de DNA/genética , Frequência do Gene/genética , Predisposição Genética para Doença , Haplótipos/genética , Humanos
19.
Plant Sci ; 283: 157-164, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128685

RESUMO

Combining ability is crucial for parent selection in crop hybrid breeding. Many studies have attempted to provide reliable and quick methods to identify genome regions in parental lines correlating with improved hybrid performance. The local haplotype patterns surrounding densely spaced DNA markers include a large amount of genetic information, and analysis of the relationships between haplotypes and hybrid performance can provide insight into the underlying genome regions which might contribute to enhancing combining ability. Here, we generated 24,403 single-copy, genome-wide SNP loci and calculated the general combining ability (GCA) of 950 hybrids from a diverse panel of 475 pollinators of spring-type canola inbred lines crossed with two testers for days to flowering (DTF) and seed glucosinolate content (GSL). We performed a genome-wide analysis of the haplotypes and detected eight and seven haplotype regions that were significantly associated with the GCA values for DTF and seed GSL, respectively. Additionally, two haplotype blocks containing orthologs of flowering time genes FLOWERING LOCUS T (FT) and FLOWERING LOCUS C (FLC) on chromosome A02 showed additive epistatic interactions influencing flowering time. Moreover, two homoeologous haplotype regions on chromosomes A02 and C02 corresponded to major quantitative trait loci (QTL) for GSL which showed additive effects related to reduction of seed GSL in F1 hybrids. Our study showed that haplotype analysis has the potential to substantially improve the efficiency of hybrid breeding programs.


Assuntos
Brassica napus/genética , Característica Quantitativa Herdável , Brassica napus/crescimento & desenvolvimento , Mapeamento Cromossômico , Flores/crescimento & desenvolvimento , Genes de Plantas/genética , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Haplótipos/genética , Vigor Híbrido/genética , Desequilíbrio de Ligação/genética , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética
20.
Lipids Health Dis ; 18(1): 110, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077198

RESUMO

Genome-wide association study (GWAS) identified chromosome 12p13 rs12425791 and rs11833579 as susceptibility loci of ischemic stroke (IS) in a European population. However, conflicting results were obtained in subsequent replication analysis. miR-200c, located on chromosome 12p13, was found to have a neuroprotective effect on ischemia. Our aim of this study was to investigate the association of the rs12425791, rs11833579 and rs12904 in the binding site of miR-200c with the risk of IS. The rs12425791, rs11833579, and rs12904 were genotyped using a TaqMan allelic discrimination assay. The results were verified by Sanger sequencing. We found that the rs12904 AG/GG genotypes and G allele were associated with a decreased risk of IS (AG/GG vs. AA: adjusted OR = 0.64; 95% CI, 0.44-0.95; G vs. A: adjusted OR = 0.65; 95% CI, 0.46-0.93). The combined genotypes of the rs11833579AG/AA and rs12904AG/GG were also associated with a reduced risk of IS (OR = 0.65; 95% CI, 0.46-0.93). These findings suggest that the rs12904 may have a jointly protective effect against the risk of IS.


Assuntos
Isquemia Encefálica/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Sítios de Ligação , Cromossomos Humanos Par 12/genética , Feminino , Estudo de Associação Genômica Ampla , Haplótipos/genética , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Fatores de Risco
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