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1.
Saija J. Ahonen Elina Pietil? Cathryn S. Mellersh Katriina Tiira Liz Hansen Gary S. Johnson Hannes Lohi 《PloS one》2013,8(8)
Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10−10, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease. 相似文献
2.
QTL analysis of white blood cell, platelet and red blood cell-related traits in an F2 intercross between Landrace and Korean native pigs 总被引:1,自引:0,他引:1
Cho IC Park HB Yoo CK Lee GJ Lim HT Lee JB Jung EJ Ko MS Lee JH Jeon JT 《Animal genetics》2011,42(6):621-626
Haematological traits play important roles in disease resistance and defence functions. The objective of this study was to locate quantitative trait loci (QTL) and the associated positional candidate genes influencing haematological traits in an F2 intercross between Landrace and Korean native pigs. Eight blood‐related traits (six erythrocyte traits, one leucocyte trait and one platelet trait) were measured in 816 F2 progeny. All experimental animals were genotyped with 173 informative microsatellite markers located throughout the pig genome. We report that nine chromosomes harboured QTL for the baseline blood parameters: genomic regions on SSC 1, 4, 5, 6, 8, 9, 11, 13 and 17. Eight of twenty identified QTL reached genome‐wide significance. In addition, we evaluated the KIT locus, an obvious candidate gene locus affecting variation in blood‐related traits. Using dense single nucleotide polymorphism marker data on SSC 8 and the marker‐assisted association test, the strong association of the KIT locus with blood phenotypes was confirmed. In conclusion, our study identified both previously reported and novel QTL affecting baseline haematological parameters in pigs. Additionally, the positional candidate genes identified here could play an important role in elucidating the genetic architecture of haematological phenotype variation in swine and in humans. 相似文献
3.
Owerbach D Piña L Gabbay KH 《Biochemical and biophysical research communications》2004,323(3):865-869
Type I diabetes is a complex disease in which multiple susceptibility loci have been implicated by whole genome scans. IDDM8, a susceptibility locus, is located on chromosome 6q27, however the specific susceptibility gene has yet to be identified. We have examined five potential candidate genes using 36 genetic markers, spanning 360kb located near the chromosome 6q27 terminus in 478 families for diabetes association. No associations with type I diabetes susceptibility were detected with the strength previously observed for IDDM1 or IDDM2. However, a novel CAG/CAA polymorphism was detected in exon 3 of the TATA box-binding protein gene, which shows preliminary evidence of association with diabetes susceptibility (p<0.05). 相似文献
4.
A search for genetic loci responsible for emotional stress-induced arterial hypertension in the ISIAH rats 总被引:2,自引:0,他引:2
Hypertension is a widespread human disease caused by a complex interaction of a series of the genetic factors with both each other and the environmental conditions. In this study we aimed at determining the candidate genetic loci responsible for hypertension in the ISIAH rats and studying the dynamics of the relevant genetic and physiological mechanisms in rat ontogeny. The candidate genetic loci were identified from association of the microsatellite markers linked to these loci with arterial hypertension in rat F2 hybrids exposed to stress. Two populations of F2 hybrids of different age (3-4 and 6 months) were obtained by crossing hypertensive ISIAH and normotensive WAG rats. We present the results of cosegregation analysis for the following loci: the gene for the Na+, K(+)-ATPase alpha 1 subunit isoform (Atp1a1), the endothelin-2 gene (Edn2), the low affinity nerve growth factor receptor gene (Lngfr), and a region of chromosome 10 marked with the D10Rat58 microsatellile located 3 cM away of the aldolase C gene (AldC). The results obtained allowed us to localize the genes responsible for the stress-induced arterial hypertension in the ISIAH rats to the Atp1a1 locus (P < 0.05), chromosome 2 and to the Lngfr gene locus (P < 0.05), chromosome 10. The association of hypertensive status with the Lngfr gene was found only in young ISIAH rats whereas in adult rats of this line, hypertension was associated with the Atp1a1 locus. 相似文献
5.
Redina O. E. Khvorostova J. V. Dymshits G. M. Markel A. L. 《Russian Journal of Genetics》2003,39(6):676-680
Hypertension is a widespread human disease caused by a complex interaction of a series of the genetic factors with both each other and the environmental conditions. In this study we aimed at determining the candidate genetic loci responsible for hypertension in the ISIAH rats and studying the dynamics of the relevant genetic and physiological mechanisms in rat ontogeny. The candidate genetic loci were identified from association of the microsatellite markers linked to these loci with arterial hypertension in rat F2 hybrids exposed to stress. Two populations of F2 hybrids of different age (3–4 and 6 months) were obtained by crossing hypertensive ISIAH and normotensive WAG rats. We present the results of cosegregation analysis for the following loci: the gene for the Na+, K+-ATPase alpha 1 subunit (Atp1a1), the endothelin-2 gene (Edn2), the low affinity nerve growth factor receptor gene (Lngfr), and a region of chromosome 10 marked with the D10Rat58 microsatellile located 3 cM away of the aldolase C gene (AldC). The results obtained allowed us to localize the genes responsible for the stress-induced arterial hypertension in the ISIAH rats to the Atp1a1locus (P < 0.05), chromosome 2 and to the Lngfr gene locus (P < 0.05), chromosome 10. The association of hypertensive status with the Lngfr gene was found only in young ISIAH rats whereas in adult rats of this strain, hypertension was associated with the Atp1a1locus. 相似文献
6.
7.
Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Sequence variations in the coding region of the prion gene (PRNP) have been associated with acquired transmissible spongiform encephalopathy (TSE) susceptibility in mammals; however, this is not the case in cattle. It has been hypothesized that genes, in addition to the prion gene, contribute to genetic susceptibility of acquired TSEs. Accordingly, genetic studies of classical BSE in cattle identified loci other than PRNP that are associated with disease incidence. The objective of this study was to utilize a genome-wide association study to test for genetic loci associated with classical BSE. The samples include 143 BSE affected (case) and 173 unaffected half sib (control) animals collected in the mid 1990s in Southern England. The data analysis identifies loci on two different chromosomes associated with BSE disease occurrence. Most notable is a single nucleotide polymorphism on chromosome 1 at 29.15 Mb that is associated with BSE disease (p = 3.09E-05). Additionally, a locus on chromosome 14, within a cluster of SNPs showed a trend toward significance (p = 5.24E-05). It is worth noting that in a human vCJD study markers on human chromosome 8, a region with shared synteny to the region identified on cattle chromosome 14, were associated with disease. Further, our candidate genes appear to have plausible biological relevance with the known etiology of TSE disease. One of the candidate genes is hypothetical gene LOC521010, similar to FK506 binding protein 2 located on chromosome 1 at 29.32 Mb. This gene encodes a protein that is a member of the immunophilin protein family and is involved in basic cellular processes including protein folding. The chromosomal regions identified in this study and candidate genes within these regions merit further investigation. 相似文献
8.
Ho-Young Son Seong-Wook Sohn Sun-Hwa Im Hyun-Jin Kim Mi Kyeong Lee Bayasgalan Gombojav Hyouk-Soo Kwon Daniel S. Park Hyung-Lae Kim Kyung-Up Min Joohon Sung Jeong-Sun Seo Jong-Il Kim 《PloS one》2015,10(10)
The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia. 相似文献
9.
Quantitative trait locus analysis for hemostasis and thrombosis 总被引:1,自引:0,他引:1
Qila Sa Erika Hart Annie E. Hill Joseph H. Nadeau Jane L. Hoover-Plow 《Mammalian genome》2008,19(6):406-412
Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study
was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding
assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5A/J, Chr11A/J
, Chr17A/J) were identified (Hmtb1, Hmtb2, Hmtb3). The tail-bleeding/rebleeding assay is widely used and distinguishes mice with genetic defects in blood clot formation or
dissolution. In the present study, quantitative trait locus (QTL) analysis revealed a significant locus for rebleeding (clot
stability) time (time between cessation of initial bleeding and start of the second bleeding) on chromosome 5, suggestive
loci for bleeding time (time between start of bleeding and cessation of bleeding) also on chromosomes 5, and two suggestive
loci for clot stability on chromosome 17 and one on chromosome 11. The three CSS and the parent A/J had elevated clot stability
time. There was no interaction of genes on chromosome 11 with genes on chromosome 5 or chromosome 17. On chromosome 17, twenty-three
candidate genes were identified in synteny with previously identified loci for thrombotic risk on human chromosome 18. Thus,
we have identified new QTLs and candidate genes not previously known to influence thrombotic risk.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
Johansson CM Zunec R García MA Scherbarth HR Tate GA Paira S Navarro SM Perandones CE Gamron S Alvarellos A Graf CE Manni J Berbotto GA Palatnik SA Catoggio LJ Battagliotti CG Sebastiani GD Migliaresi S Galeazzi M Pons-Estel BA Alarcón-Riquelme ME;Collaborative Group on the Genetics of SLE;Argentine Collaborative Group 《Human genetics》2004,115(3):230-238
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z=3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.A list of members of the Collaborative Group on the Genetics of SLE and the Argentine Collaborative Group is given in the AppendixBernardo Pons-Estel is the coordinator of the Argentine Collaborative Group 相似文献
11.
Vinicius M. Fava Monica Dallmann-Sauer Marianna Orlova Wilian Correa-Macedo Nguyen Van Thuc Vu Hong Thai Alexandre Alcaïs Laurent Abel Aurlie Cobat Erwin Schurr 《PLoS neglected tropical diseases》2021,15(12)
Leprosy is the second most prevalent mycobacterial disease globally. Despite the existence of an effective therapy, leprosy incidence has consistently remained above 200,000 cases per year since 2010. Numerous host genetic factors have been identified for leprosy that contribute to the persistently high case numbers. In the past decade, genetic epidemiology approaches, including genome-wide association studies (GWAS), identified more than 30 loci contributing to leprosy susceptibility. However, GWAS loci commonly encompass multiple genes, which poses a challenge to define causal candidates for each locus. To address this problem, we hypothesized that genes contributing to leprosy susceptibility differ in their frequencies of rare protein-altering variants between cases and controls. Using deep resequencing we assessed protein-coding variants for 34 genes located in GWAS or linkage loci in 555 Vietnamese leprosy cases and 500 healthy controls. We observed 234 nonsynonymous mutations in the targeted genes. A significant depletion of protein-altering variants was detected for the IL18R1 and BCL10 genes in leprosy cases. The IL18R1 gene is clustered with IL18RAP and IL1RL1 in the leprosy GWAS locus on chromosome 2q12.1. Moreover, in a recent GWAS we identified an HLA-independent signal of association with leprosy on chromosome 6p21. Here, we report amino acid changes in the CDSN and PSORS1C2 genes depleted in leprosy cases, indicating them as candidate genes in the chromosome 6p21 locus. Our results show that deep resequencing can identify leprosy candidate susceptibility genes that had been missed by classic linkage and association approaches. 相似文献
12.
Richard C. Davis Atila van Nas Brian Bennett Luz Orozco Calvin Pan Christoph D. Rau Eleazar Eskin Aldons J. Lusis 《Mammalian genome》2013,24(3-4):105-118
Genetic variations in blood cell parameters can impact clinical traits. We report here the mapping of blood cell traits in a panel of 100 inbred strains of mice of the Hybrid Mouse Diversity Panel (HMDP) using genome-wide association (GWA). We replicated a locus previously identified in using linkage analysis in several genetic crosses for mean corpuscular volume (MCV) and a number of other red blood cell traits on distal chromosome 7. Our peak for SNP association to MCV occurred in a linkage disequilibrium (LD) block spanning from 109.38 to 111.75 Mb that includes Hbb-b1, the likely causal gene. Altogether, we identified five loci controlling red blood cell traits (on chromosomes 1, 7, 11, 12, and 16), and four of these correspond to loci for red blood cell traits reported in a recent human GWA study. For white blood cells, including granulocytes, monocytes, and lymphocytes, a total of six significant loci were identified on chromosomes 1, 6, 8, 11, 12, and 15. An average of ten candidate genes were found at each locus and those were prioritized by examining functional variants in the HMDP such as missense and expression variants. These results provide intermediate phenotypes and candidate loci for genetic studies of atherosclerosis and cancer as well as inflammatory and immune disorders in mice. 相似文献
13.
Liljander M Sällström MA Andersson S Andersson A Holmdahl R Mattsson R 《Arthritis research & therapy》2006,8(2):R45-6
Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities
to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification
of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present
study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between
NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset,
incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite
markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset
on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance
associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant
quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates
that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy
failure. 相似文献
14.
Fine mapping and SNP analysis of positional candidates at the preeclampsia susceptibility locus (PREG1) on chromosome 2 总被引:2,自引:0,他引:2
Fitzpatrick E Göring HH Liu H Borg A Forrest S Cooper DW Brennecke SP Moses EK 《Human biology; an international record of research》2004,76(6):849-862
Genome scans in Icelandic, Australian and New Zealand, and Finnish families have localized putative susceptibility loci for preeclampsia/ eclampsia to chromosome 2. The locus mapped in the Australian and New Zealand study (designated PREG1) was thought to be the same locus as that identified in the Icelandic study. In both these studies, two distinct quantitative trait locus (QTL) regions were evident on chromosome 2. Here, we describe our fine mapping of the PREG1 locus and a genetic analysis of two positional candidate genes. Twenty-five additional microsatellite markers were genotyped within the 74-cM linkage region defined by the combined Icelandic and Australian and New Zealand genome scans. The overall position and shape of the localization evidence obtained using nonparametric multipoint analysis did not change from that seen previously in our 10-cM resolution genome scan; two peaks were displayed, one on chromosome 2p at marker D2S388 (107.46 cM) and the other on chromosome 2q at 151.5 cM at marker D2S2313. Using the robust two-point linkage analysis implemented in the Analyze program, all 25 markers gave positive LOD scores with significant evidence of linkage being seen at marker D2S2313 (151.5 cM), achieving a LOD score of 3.37 under a strict diagnostic model. Suggestive evidence of linkage was seen at marker D2S388 (107.46 cM) with a LOD score of 2.22 under the general diagnostic model. Two candidate genes beneath the peak on chromosome 2p were selected for further analysis using public single nucleotide polymorphisms (SNPs) within these genes. Maximum LOD scores were obtained for an SNP in TACR1 (LOD = 3.5) and for an SNP in TCF7L1 (LOD = 3.33), both achieving genome-wide significance. However, no evidence of association was seen with any of the markers tested. These data strongly support the presence of a susceptibility gene on chromosome 2p11-12 and substantiate the possibility of a second locus on chromosome 2q23. 相似文献
15.
Loci and candidate gene identification for resistance to Sclerotinia sclerotiorum in soybean (Glycine max L. Merr.) via association and linkage maps
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Yinghui Li Dongyuan Liu Mingming Sun Yue Zhao Chunmei Lv Dongmei Li Zhijiang Yang Long Huang Weili Teng Lijuan Qiu Hongkun Zheng Wenbin Li 《The Plant journal : for cell and molecular biology》2015,82(2):245-255
Soybean white mold (SWM), caused by Sclerotinia sclerotiorum ((Lib.) W. Phillips), is currently considered to be the second most important cause of soybean yield loss due to disease. Research is needed to identify SWM‐resistant germplasm and gain a better understanding of the genetic and molecular basis of SWM resistance in soybean. Stem pigmentation after treatment with oxaloacetic acid is an effective indicator of resistance to SWM. A total of 128 recombinant inbred lines (RILs) derived from a cross of ‘Maple Arrow’ (partial resistant to SWM) and ‘Hefeng 25’ (susceptible) and 330 diverse soybean cultivars were screened for the soluble pigment concentration of their stems, which were treated with oxalic acid. Four quantitative trait loci (QTLs) underlying soluble pigment concentration were detected by linkage mapping of the RILs. Three hundred and thirty soybean cultivars were sequenced using the whole‐genome encompassing approach and 25 179 single‐nucleotide polymorphisms (SNPs) were detected for the fine mapping of SWM resistance genes by genome‐wide association studies. Three out of five SNP markers representing a linkage disequilibrium (LD) block and a single locus on chromosome 13 (Gm13) were significantly associated with the soluble pigment content of stems. Three more SNPs that represented three minor QTLs for the soluble pigment content of stems were identified on another three chromosomes by association mapping. A major locus with the largest effect on Gm13 was found both by linkage and association mapping. Four potential candidate genes involved in disease response or the anthocyanin biosynthesis pathway were identified at the locus near the significant SNPs (<60 kbp). The beneficial allele and candidate genes should be useful in soybean breeding for improving resistance to SWM. 相似文献
16.
Matteo Bianchi Stina Dahlgren Jonathan Massey Elisabeth Dietschi Marcin Kierczak Martine Lund-Ziener Katarina Sundberg Stein Istre Thoresen Olle K?mpe G?ran Andersson William E. R. Ollier ?ke Hedhammar Tosso Leeb Kerstin Lindblad-Toh Lorna J. Kennedy Frode Lingaas Gerli Rosengren Pielberg 《PloS one》2015,10(8)
Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans. 相似文献
17.
Comabella M Craig DW Camiña-Tato M Morcillo C Lopez C Navarro A Rio J;BiomarkerMS Study Group Montalban X Martin R 《PloS one》2008,3(10):e3490
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease. 相似文献
18.
Ming Liao Dianchun Shi Yao Wang Kai Zhang Xin Chen Yong Gao Aihua Tan Qiang Xuan Xiaobo Yang Yanlin Hu Xue Qin Haiying Zhang Zengnan Mo 《Immunogenetics》2013,65(8):561-568
Immunoglobulin E (IgE) provides important information on the humoral immune status, and the IgE level is routinely detected in clinical practice. There are many diseases associated with IgE, such as atopic disease, autoimmune diseases, and so on. IgE is a genetically complex trait, but comprehensive genetic assessment of the variability in serum IgE levels is lacking. Previous genome-wide association studies (GWAS) on total serum IgE levels have identified FCER1A as the susceptibility locus; however, the candidate gene association study in southern Chinese patients reported no association. Given the genetic difference in different populations, we firstly conducted this two-stage GWAS in a Chinese population of 3,495 men, including 1,999 unrelated subjects in the first stage and 1,496 independent individuals replicated in the second stage. In the first stage, we totally identified three single nucleotide polymorphisms (SNPs) which reached a P value of 1.0?×?10?5. Rs17090302 on chromosome 3 and Rs28708846 on chromosome 13 are intergenic. Rs432085 from chromosome 3p28 is located in the gene CCDC50. When the two-stage data was combined, none of the SNPs reached the genome-wide significant level. Collectively, we did not identify novel loci associated with the serum IgE level in Chinese males, but we hypothesized that CCDC50 was a candidate gene in regulation on IgE level. 相似文献
19.
Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania,Australia 总被引:2,自引:0,他引:2
The minimum physical distance surrounding a candidate gene has been determined in founder populations by studying allele sharing and then mapping historical recombination events. In this study, we developed a novel minimalistic approach by using the genetically isolated population of Tasmania, Australia, to identify candidate gene loci in a small number of individuals of unknown genetic relationship affected by a dominant disorder. Keratoconus, an inheritable non-inflammatory progressive degeneration of the cornea, is present at a five-fold increased incidence in Burnie, a coastal town on the island of Tasmania. Based on the fundamental assumption that individuals with keratoconus from this town are likely to be related through a founder effect, a 10-cM interval genome scan was conducted on six patients of undefined genetic relationship and one affected sib-pair to identify commonly shared chromosomal segments for the elucidation of candidate gene loci. Analysis of allele sharing revealed four markers on three chromosomes where all eight individuals shared a common allele on at least one chromosome, and thirteen markers where all but one patient shared common alleles. No excess of allele sharing was observed at any marker tested on chromosome 21, a suggested candidate chromosome for keratoconus. Further analysis of positive loci revealed suggestive association at 20q12, where significant deviation in allele frequency D20S119 ( P=2.1 x 10(-5)) is observed when additional Tasmanian keratoconus samples are genotyped. Identification of a conserved minimal chromosomal haplotype around D20S119 in related Tasmanian patients suggests association with this locus, however association with the nearby candidate gene MMP-9 has been excluded. 相似文献
20.
Anna W. Santure Isabelle De Cauwer Matthew R. Robinson Jocelyn Poissant Ben C. Sheldon Jon Slate 《Molecular ecology》2013,22(15):3949-3962
Clutch size and egg mass are life history traits that have been extensively studied in wild bird populations, as life history theory predicts a negative trade‐off between them, either at the phenotypic or at the genetic level. Here, we analyse the genomic architecture of these heritable traits in a wild great tit (Parus major) population, using three marker‐based approaches – chromosome partitioning, quantitative trait locus (QTL) mapping and a genome‐wide association study (GWAS). The variance explained by each great tit chromosome scales with predicted chromosome size, no location in the genome contains genome‐wide significant QTL, and no individual SNPs are associated with a large proportion of phenotypic variation, all of which may suggest that variation in both traits is due to many loci of small effect, located across the genome. There is no evidence that any regions of the genome contribute significantly to both traits, which combined with a small, nonsignificant negative genetic covariance between the traits, suggests the absence of genetic constraints on the independent evolution of these traits. Our findings support the hypothesis that variation in life history traits in natural populations is likely to be determined by many loci of small effect spread throughout the genome, which are subject to continued input of variation by mutation and migration, although we cannot exclude the possibility of an additional input of major effect genes influencing either trait. 相似文献