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1.
When activated, thrombin activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis by modifying fibrin, depressing its plasminogen binding potential. Polymorphisms in the TAFI structural gene (CPB2) have been associated with variation in TAFI levels, but the potential occurrence of influential quantitative trait loci (QTLs) located elsewhere in the genome has been explored only in families ascertained in part through probands affected by thrombosis. We report the results of the first genome-wide linkage screen for QTLs that influence TAFI phenotypes. Data are from 635 subjects from 21 randomly ascertained Mexican American families participating in the San Antonio Family Heart Study. Potential QTLs were localized through a genome-wide multipoint linkage scan using 417 highly informative autosomal short tandem repeat markers spaced at approximately 10-cM intervals. We observed a maximum multipoint LOD score of 3.09 on chromosome 13q, the region of the TAFI structural gene. A suggestive linkage signal (LOD = 2.04) also was observed in this region, but may be an artifact. In addition, weak evidence for linkage occurred on chromosomes 17p and 9q. Our results suggest that polymorphisms in the TAFI structural gene or its nearby regulatory elements may contribute strongly to TAFI level variation in the general population, although several genes in other regions of the genome may also influence variation in this phenotype. Our findings support those of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project, which identified a potential TAFI QTL on chromosome 13q in a genome-wide linkage scan in Spanish thrombophilia families.  相似文献   

2.
Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ–VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a genome-scan of 387 micro-satellite markers in 210 families augmented with additional markers added in a subset of families. Empirical P values were calculated for five interesting regions. Linkage analysis identified five chromosomal regions with substantial regional evidence of linkage; 10p12 [P = 0.001; genome-wide (gw) P = 0.05], 16q23 (P = 0.015; gw P = 0.53), 2p21 (P = 0.03, gw P = 0.78), 6q25 (P = 0.047, gw P = 0.91) and 15q23-25 (P = 0.053, gw P = 0.93). The location of the chromosome 10 linkage signal coincides with a region noted in a much earlier genome-scan for autism, and the chromosome 16 signal coincides exactly with a linkage signal for non-word repetition in specific language impairment. This study provides strong evidence for a QTL influencing IQ discrepancy in families with autistic individuals on chromosome 10, and suggestive evidence for a QTL on chromosome 16. The location of the chromosome 16 signal suggests a candidate gene, CDH13, a T-cadherin expressed in the brain, which has been implicated in previous SNP studies of autism and ADHD.  相似文献   

3.
Despite extensive research of genetic determinants of human adult height, the genes identified up until now allow to predict only a small proportion of the trait’s variance. To identify new genes we analyzed 2,486 genotyped and phenotyped individuals in a large pedigree including 23,612 members in 18 generations. The pedigree was derived from a young genetically isolated Dutch population, where genetic heterogeneity is expected to be low and linkage disequilibrium has been shown to be increased. Complex segregation analysis confirmed high heritability of adult height, and suggested mixed model of height inheritance in this population. The estimates of the model parameters obtained from complex segregation analysis were used in parametric linkage analysis, which highlighted three genome-wide significant and additionally at least four suggestive loci involved in height. Significant peaks were located at the chromosomal regions 1p32 (LOD score = 3.35), 2p16 (LOD score = 3.29) and 16q24 (LOD score = 3.94). For the latter region, a strong association signal (FDR q < 0.05) was obtained for 19 SNPs, 17 of them were located in the CDH13 (cadherin 13) gene of which one (rs1035569) explained 1.5% of the total height variance.  相似文献   

4.
Binge eating is a heritable trait associated with eating disorders and refers to the rapid consumption of a large quantity of energy-dense food that is, associated with loss of control and negative affect. Binge eating disorder is the most common eating disorder in the United States; however, the genetic basis is unknown. We previously identified robust mouse inbred strain differences between C57BL/6J and DBA/2J in binge-like eating of sweetened palatable food in an intermittent access, conditioned place preference paradigm. To map the genetic basis of changes in body weight and binge-like eating (BLE) and to identify candidate genes, we conducted quantitative trait locus (QTL) analysis in 128 C57BL/6J x DBA/2J-F2 mice combined with PheQTL and trait covariance analysis in GeneNetwork2 using legacy BXD-RI trait datasets. We identified a QTL on Chromosome 18 influencing changes in body weight across days in females (log of the odds [LOD] = 6.3; 1.5-LOD: 3–12 cM) that contains the candidate gene Zeb1. We also identified a sex-combined QTL influencing initial palatable food intake on Chromosome 5 (LOD = 5.8; 1.5-LOD: 21–28 cM) that contains the candidate gene Lcorl and a second QTL influencing escalated palatable food intake on Chromosome 6 in males (LOD = 5.4; 1.5-LOD: 50–59 cM) that contains the candidate genes Adipor2 and Plxnd1. Finally, we identified a suggestive QTL in females for slope of BLE on distal Chromosome 18 (LOD = 4.1; p = 0.055; 1.5-LOD: 23–35 cM). Future studies will use BXD-RI strains to fine map loci and support candidate gene nomination for gene editing.  相似文献   

5.
Information on genetic variation and its distribution in tropical plant populations relies mainly on studies of ground‐rooted species, while genetic information of epiphytic plants is still limited. Particularly, the effect of forest successional condition on genetic diversity and structure of epiphytes is scanty in the literature. We evaluated the genetic variation and spatial genetic structure of the epiphytic bromeliad Guzmania monostachia (Bromeliaceae, Tillandsioideae) in montane secondary forest patches in Costa Rica. The sampling design included plants on the same trees (i.e., populations), populations within forest patches and patches within secondary forest at two different successional stages (early vs. mid‐succession). Six microsatellites revealed low levels of population genetic variation (A = 2.06, AE = 1.61, HE = 0.348), a marked deficiency of heterozygotes (HO = 0.031) and high inbreeding (f = 0.908). Genetic differentiation was negligible among populations within the same forest patch, but moderate (GST = 0.123 ± 0.043) among forest patches. Genetic relatedness between individuals was significantly higher for plants located within the same forest patch and separated by <60 m and decreased as distance between plants increased, becoming significantly negative at distances >400 m. An analysis of molecular variance (AMOVA) showed significant genetic variation between forest patches, but non‐significant variation between successional stages. The selfing breeding system and limited seed dispersal capabilities in G. monostachia could explain the observed levels and partitioning of genetic diversity at this geographic scale. However, these results also suggest that forest fragmentation is likely to influence the degree of local genetic structuring of epiphytic plants by limiting gene flow.  相似文献   

6.
Although obesity is more prevalent in Hispanics than non-Hispanic whites in the United States, little is known about the genetic etiology of the related traits in this population. To identify genetic loci influencing obesity in non-Mexican Hispanics, we performed a genome-wide linkage scan in 1,390 subjects from 100 Caribbean Hispanic families on six obesity-related quantitative traits: body mass index (BMI), body weight, waist circumference, waist-to-hip ratio, abdominal and average triceps skinfold thickness after adjusting for significant demographic and lifestyle factors. We then carried out an association analysis of the linkage peaks and the FTO gene in an independent community-based Hispanic subcohort (N = 652, 64% Caribbean Hispanics) from the Northern Manhattan Study. Evidence of linkage was strongest on 1q43 with multipoint LOD score of 2.45 (p = 0.0004) for body weight. Suggestive linkage evidence of LOD > 2.0 was also identified on 1q43 for BMI (LOD = 2.03), 14q32 for abdominal skinfold thickness (LOD = 2.17), 16p12 for BMI (LOD = 2.27) and weight (LOD = 2.26), and 16q23–24 for average triceps skinfold thickness (LOD = 2.32). In the association analysis of 6,440 single nucleotide polymorphisms (SNPs) under 1-LOD unit down regions of our linkage peaks on chromosome 1q43 and 16p12 as well as in the FTO gene, we found that two SNPs (rs6665519 and rs669231) on 1q43 and one FTO SNP (rs12447427) were significantly associated with BMI or body weight after adjustment for multiple testing. Our results suggest that in addition to FTO, multiple genetic loci, particularly those on 1q43 region, may contribute to the variations in obesity-related quantitative traits in Caribbean Hispanics.  相似文献   

7.
Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non‐liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck × mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome‐wide association studies were conducted. A region of about 1.5 Mb (21.8–23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (?logP = 21.45) and 8 weeks (?logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.  相似文献   

8.
Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p = 1.82e-05). We identified a QTL on Chromosome 2 (LOD = 2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD = 3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD = 2.67), whereas in males a QTL was identified on Chromosome 1 (LOD = 2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene MRPL37, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene CMPK2, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels.  相似文献   

9.
Spawning aggregations of Pacific herring (Clupea pallasi) often exhibit significant interannual variation in allele frequencies of neutral gene markers. We isolated 14 tetranucleotide microsatellites to examine hypothetical processes that may produce this unique genetic signal. We developed and tested primer pairs for each locus and then estimated locus variability in samples (n = 60) from two populations. The number of alleles per locus ranged from five to 49. The expected heterozygosity across loci and populations ranged from 0.20 to 0.96. These microsatellites will be useful for estimating genetic variation in herring on a fine geographical scale.  相似文献   

10.
Folate is crucial for various cellular functions. Several transport mechanisms allow folate to enter the intracellular compartment with folate receptor-α being the major high-affinity receptor. Rare genetic variations in exons of the FR-α gene, FOLR1, were recently shown to cause severe folate deficiency accompanied by neurological and other disturbances. So far, similar effects by genetic variation in noncoding parts of the FOLR1 gene have not been identified. The aim of our study was to determine biochemically the haplotype structure of two linked polymorphisms in the FOLR1 gene, 1816delC and 1841G>A, the prevalences of the mutated alleles across Eurasia, and their possible effects on physiological folate levels in vivo. For this purpose we employed allele-specific PCR and Pyrosequencing technology and performed genotyping in 738 subjects from Spain, 387 from Sweden, 952 from Estonia, and 47 from Korea. We demonstrate the presence of an ancient double-mutated haplotype 1816delC–1841A in the FOLR1 gene, with the prevalence of the mutated allele being highest among Koreans (q = 0.074), lower in Estonians (q = 0.017), Spaniards (q = 0.0061), and the lowest among Swedes (q = 0.0026). Erythrocyte folate levels were studied in the Spanish population sample, where subjects carrying the double-mutated FOLR1 haplotype had significantly reduced levels by 27% (P = 0.039), adjusted for serum vitamin B12 levels and MTHFR 677C>T genotype, while the mean serum folate levels were only 20% lower among the carriers (P = 0.11). Plasma homocysteine and cobalamin levels did not differ. Thus, we have demonstrated by molecular haplotyping an ancient double-mutated haplotype 1816delC–1841A in the FOLR1 gene, spread over the whole Eurasian continent, which may be of functional importance for uptake of folate in red blood cells.  相似文献   

11.
Switchgrass (Panicum virgatum L.) is an important crop for bioenergy feedstock development. Switchgrass has two main ecotypes: the lowland ecotype being exclusively tetraploid (2n = 4x = 36) and the upland ecotype being mainly tetraploid and octaploid (2n = 8x = 72). Because there is a significant difference in ploidy, morphology, growth pattern, and zone of adaptation between and within the upland and lowland ecotypes, it is important to discriminate switchgrass plants belonging to different genetic pools. We used 55 simple sequence repeats (SSR) loci and six chloroplast sequences to identify patterns of variation between and within 18 switchgrass cultivars representing seven lowland and 11 upland cultivars from different geographic regions and of varying ploidy levels. We report consistent discrimination of switchgrass cultivars into ecotype membership and demonstrate unambiguous molecular differentiation among switchgrass ploidy levels using genetic markers. Also, SSR and chloroplast markers identified genetic pools related to the geographic origin of the 18 cultivars with respect to ecotype, ploidy, and geographical, and cultivar sources. SSR loci were highly informative for cultivar fingerprinting and to classify plants of unknown origin. This classification system is the first step toward developing switchgrass complementary gene pools that can be expected to provide a significant heterotic increase in biomass yield.  相似文献   

12.
《Aquatic Botany》2007,86(1):46-52
Vallisneria spinulosa is a dominant submerged macrophyte in lakes of the middle–lower reaches of the Yangtze River. Allozyme variation, clonal diversity and population genetic structure were investigated for a total of 396 individuals sampled from 10 extant populations. V. spinulosa maintained high levels of genetic variation both at the species (P = 46.2, A = 1.69, He = 0.23) and at the population level (P = 46.2, A = 1.58, He = 0.21). Although aquatic macrophytes commonly exhibit low genetic variation within populations, the obligately outcrossing mating system of V. spinulosa and pervasive gene flow likely account for the high levels of diversity maintained within populations. All V. spinulosa populations contained high clonal diversity with a mean proportion of distinguishable genotypes of 0.57 and a mean Simpson's diversity index of 0.95, indicating that populations were founded sexually or that successful seedling recruitment occurred after initial colonization. Partitioning of genetic diversity revealed a surprisingly low population differentiation (GST = 0.06) as compared to other hydrophilous angiosperms. No evidence of isolation-by-distance was found (r = 0.056, P = 0.312), suggesting that gene flow was not restricted geographically. The UPGMA cluster analysis revealed that several widely separated populations grouped together, suggesting long-distance gene flow among populations. The high vagility of V. spinulosa and extensive hydrologic connectivity among populations have facilitated long-distance gene flow and resulted in the pattern of population genetic structure in V. spinulosa.  相似文献   

13.
We quantified population connectivity and genetic variation in the Marco Polo subspecies of argali mountain sheep (Ovis ammon polii) by genotyping 9 neutral and 8 candidate gene microsatellite loci in 172 individuals noninvasively sampled across five study areas in Afghanistan, China, and Tajikistan. Heterozygosity and allelic richness were generally high (mean H = 0.67, mean A = 6.1), but were significantly lower in the China study area (H = 0.61, P < 0.001; A = 4.9, P < 0.01). One marker in an immune system gene (TCRG4) showed an excess of rare alleles compared to neutral expectations. Another immune system gene (GLYCAM-1) showed excessive differentiation (high F ST) between study areas. Estimates of genetic differentiation were similar (F ST = 0.035 vs. 0.033) with and without the two loci deviating from neutrality, suggesting that selection is not a primary driver of overall molecular variation, and that candidate gene loci can be used for connectivity monitoring, as long as selection tests are conducted to avoid biased gene flow estimates. Adequate protection of argali and maintenance of inter-population connectivity will require monitoring and international cooperation because argali exhibit high gene flow across international borders.  相似文献   

14.
Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs3734016, P uncorr = 0.009) and for the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782, P uncorr = 0.004). In the Norwegian cohort we identified evidence of a genetic association for ERAP1 (rs34750, P uncorr = 0.011) and for ERAP2 (rs17408150, P uncorr = 0.009). The ERAP2 SNPs in both cohorts remained statistically significant (rs2549782, P corr = 0.018; rs17408150, P corr = 0.039) after corrections at an experiment-wide level. The ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood pressure regulation and essential hypertension in addition to innate immune and inflammatory responses. Perturbations within vascular, immunological and inflammatory pathways constitute important physiological mechanisms in preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder.  相似文献   

15.
Miscanthus lutarioriparius is an endemic species that grows along the middle and lower reaches of the Yangtze River and is a valuable source of germplasm for the development of second‐generation energy crops. The plant that propagates via seeds, stem nodes, and rhizomes shows high phenotypic variation and strong local adaptation. Here, we examined the magnitude and spatial distribution of genetic variation in M. lutarioriparius across its entire distributional range and tested underlying factors that shaped its genetic variation. Population genetic analyses were conducted on 644 individuals from 25 populations using 16 microsatellite markers. M. lutarioriparius exhibited a high level of genetic variation (HE = 0.682–0.786; A= 4.74–8.06) and a low differentiation (FST = 0.063; Dest = 0.153). Of the total genetic variation, 10% was attributed to the differences among populations (df = 24, < 0.0001), whereas 90% was attributed to the differences among individuals (df = 619, ≤ 0.0001). Genetic diversity did not differ significantly across longitudes and did not increase in the populations growing downstream of the Yangtze River. However, significant associations were found between genetic differentiation and spatial distance. Six genetic discontinuities were identified, which mostly distributed among downstream populations. We conclude that anthropogenic factors and landscape features both contributed to shaping the pattern of gene flow in M. lutarioriparius, including long‐distance bidirectional dispersal. Our results explain the genetic basis of the high degree of adaptability in M. lutarioriparius and identify potential sources of new germplasm for the domestication of this potential second‐generation energy crop.  相似文献   

16.
Understanding how abiotic factors influence the spatial distribution of genetic variation provides insight into microevolutionary processes. The intertidal seascape is characterized by highly heterogeneous habitats which probably influence the partitioning of genetic variation at very small scales. The effects of tidal height on genetic variation in both the haploid (gametophytes) and diploid (tetrasporophytes) stages of the red alga Chondrus crispus were studied. Fronds were sampled every 25 cm within a 5 m × 5 m grid and along a 90-m transect at two shore heights (high and low) in one intertidal site in France. The multilocus genotype of 799 fronds was determined (Nhaploid = 586; Ndiploid = 213) using eight microsatellite loci to test the following hypotheses: (i) high and low shore fronds belong to genetically differentiated populations, (ii) gene flow is restricted within the high shore habitat due to tidal-influenced isolation and (iii) significant FIS values are driven by life history characteristics. Pairwise FST estimates between high and low shore levels supported the hypothesis that high and low shore fronds were genetically differentiated. The high shore was characterized by the occurrence of within-shore genetic differentiation, reduced genetic diversity and increased levels of intergametophytic selfing, suggesting it is a marginal environment. These results suggest at fine scales within the intertidal seascape the same mechanisms as those over the species’ distributional range are at work with core and marginal population dynamics.  相似文献   

17.
The Florida grasshopper sparrow, Ammodramus savannarum floridanus, is a non-migratory, endangered subspecies endemic to the prairie region of south-central Florida. It has experienced significant population declines and is currently restricted to five locations. We found substantial levels of variation in microsatellites and mtDNA control region sequences, estimates of inbreeding genetic effective population sizes that were much larger than the estimated census size, and no evidence of inbreeding within five sampled populations (n = 105). We also found a lack of genetic structure among populations (F ST = 0.0123 for microsatellites and θ = 0.008 for mtDNA), and evidence for dispersal between populations, with 7.6% of all individuals identified as immigrants to their population of capture. We suggest that the subspecies be managed as a single management unit on a regional scale rather than as multiple management units on a local subpopulation scale. There is still a limited opportunity to preserve much of the present genetic variation in this subspecies, if immediate measures are taken to reverse the current population decline before this variation is reduced by genetic drift.  相似文献   

18.
He J  Chen L  Si Y  Huang B  Ban X  Wang Y 《Genetica》2009,135(2):233-243
Magnolia officinalis subsp. biloba, a traditional Chinese medicinal plant, experienced severe declines in the number of populations and the number of individuals in the late 20th century due to the widespread harvest of the subspecies. A large-scale cultivation program was initiated and cultivated populations rapidly recovered the loss in individual plant numbers, but wild populations remained small as a consequence of cutting. In this study, the levels of genetic variation and genetic structure of seven wild populations and five domestic populations of M. officinalis subsp. biloba were estimated employing an AFLP methodology. The plant exhibited a relatively high level of intra-population genetic diversity (h = 0.208 and H j = 0.268). The cultivated populations maintained approximately 95% of the variation exhibited in wild populations, indicating a slight genetic bottleneck in the cultivated populations. The analysis of genetic differentiation revealed that most of the AFLP diversity resided within populations both for the wild group (78.22%) and the cultivated group (85.92%). Genetic differentiation among populations in the wild group was significant (F ST = 0.1092, P < 0.005), suggesting wild population level genetic structure. Principal coordinates analysis (PCO) did not discern among wild and cultivated populations, indicating that alleles from the wild population were maintained in the cultivated gene pool. Results from the present study provide important baseline data for effectively conserving the genetic resources of this medicinal subspecies.  相似文献   

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