邓红文
以复杂性状与疾病为研究对象,以遗传与突变为研究的核心问题,从事了进化生物学、分子进化遗传学、群体及数量遗传学、生态遗传学、骨医学、骨质分子遗传学、计算和统计遗传学等跨学科和交叉学科的研究。
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- 姓名:邓红文
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博士生导师
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光学
- 研究兴趣:以复杂性状与疾病为研究对象,以遗传与突变为研究的核心问题,从事了进化生物学、分子进化遗传学、群体及数量遗传学、生态遗传学、骨医学、骨质分子遗传学、计算和统计遗传学等跨学科和交叉学科的研究。
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【期刊论文】A Genomewide Linkage Scan for Quantitative-Trait Loci for Obesity Phenotypes
邓红文, Hong-Wen Deng, , Hongyi Deng, Yong-Jun Liu, Yao-Zhong Liu, Fu-Hua Xu, Hui Shen, Theresa Conway, Jin-Long Li, Qing-Yang Huang, K.M. Davies, and Robert R. Recker
Am. J. Hum. Genet. 70:1138-1151, 2002,-0001,():
-1年11月30日
Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains 110,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome linkage scan, using 380 microsatellite markers to identify genomic regions that may contain quantitative-trait loci (QTLs) for obesity. Each pedigree was ascertained through a proband who has extremely low bone mass, which translates into a low BMI. A major QTL for BMI was identified on 2q14 near the marker D2S347 with a LOD score of 4.04 in twopoint analysis and a maximum LOD score (MLS) of 4.44 in multipoint analysis. The genomic region near 2q14 also achieved an MLS 12.0 for percentage of fat mass and body fat mass. For the putative QTL on 2q14, as much as 28.2% of BMI variation (after adjustment for age and sex) may be attributable to this locus. In addition, several other genomic regions that may contain obesity-related QTLs are suggested. For example, 1p36 near the marker D1S468 may contain a QTL for BMI variation, with a LOD score of 2.75 in two-point analysis and an MLS of 2.09 in multipoint analysis. The genomic regions identified in this and earlier reports are compared for further exploration in extension studies that use larger samples and/or denser markers for confirmation and fine-mapping studies, to eventually identify major functional genes involved in obesity.
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邓红文, Shu-Feng Lei
Hum Genet (2005)116:200-207,-0001,():
-1年11月30日
Collagen type Ia2 (COL1A2) and parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1) are two prominent candidate genes for bone mineral density (BMD). To test their importance for BMD variation in Chinese, we recruited 388 nuclear families composed of both parents and at least one healthy daughter with a total of 1,220 individuals, and simultaneously analyzed population stratification, total-family association, and within-family association between BMD at the spine and hip and the (GT)n marker in the intron 1 of the COL1A2 gene and the (AAAG)n marker in the P3 promoter of PTHR1 gene. We also performed these association analyses with haplotypes of the MspI and (GT)n polymorphisms in the COL1A2 gene. Significant within-family association was found between the M(GT)12 haplotype and trochanter BMD (P<0.001). Individuals with this haplotype have, on average, 9.53% lower trochanter BMD than the non-carriers. Suggestive evidence of the within-family association was detected between the (GT)17 allele and BMD at the spine (P=0.012), hip (P=0.011), femoral neck (P=0.032), trochanter (P=0.023), and intertrochanter (P=0.034). The association was confirmed by subsequent permutation tests. For the association, the proportion of phenotypic variance explained by the detected markers ranged from 1.2 to 3.9%, with the highest 3.9% at the trochanter for the M(GT)12 haplotype. This association indicates that there is strong linkage disequilibrium between the polymorphisms (MspI and GT repeat polymorphism) in the COL1A2 gene and a nearby quantitative trait locus (QTL) underlying BMD variation in Chinese, or the markers themselves may have an important effect on the variation of BMD. On the other hand, no significant within-family association, population stratification and total-family association between the PTHR1 polymorphism and BMD were found in our Chinese population.
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邓红文, Hong-Wen Deng, , *, Hui Shen, Fu-Hua Xu, Hongyi Deng, Theresa Conway, Yong-Jun Liu, Yao-Zhong Liu, Jin-Long Li, Qing-Yang Huang, K.M. Davies, and Robert R. Recker
American Journal of Medical Genetics 119A:121-131(2003),-0001,():
-1年11月30日
Bone size is an important determinant of osteoporotic fractures. For a sample of 53 pedigrees that contains more than 10,000 relative pairs informative for linkage analyses, we performed a whole-genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain QTLs of bone size (two-dimensional measurement by dual energy X-ray absorptiometry). We conducted two- and multi-point linkage analyses. Several potentially important genomic regions were identified. For example, the genomic region 17q23 may contain a QTL for wrist (ultra distal) bone size variation; a LOD score of 3.98 is achieved at D17S787 in two-point analyses and a maximum LOD score (MLS) of 3.01 is achieved in multi-point analyses in 17q23. 19p13 may contain a QTL for hip bone size variation; a LOD score of 1.99 is achieved at D19S226 in two-point analyses and a MLS of 2.83 is achieved in 19p13 in multi-point analyses. The genomic region identified on chromosome 17 for wrist bone size seems to be consistent with that identified for femur head width variation in an earlier wholegenome scan study. The genomic regions identified in this study and an earlier investigation on one-dimensional bone size measurement by radiography are compared. The two studies may form a basis for further exploration with larger samples and/or denser markers for confirmation and fine mapping studies to eventually identify major functional genes and the associated causes for osteoporosis.
bone size, linkage, osteoporosis, pedigrees, wholegenome scan
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邓红文, Jin-Long Li, , Hongyi Deng, Dong-Bing Lai, Fuhua Xu, Jian Chen, Guimin Gao, Robert R. Recker, and Hong-Wen Deng
Cenome Research 11:1304-1314,-0001,():
-1年11月30日
To efficiently manipulate large amounts of genotype data generated with fluorescently labeled dinucleotide markers, we developed a Microsoft Access database management system, named GenoDB. GenoDB offers several advantages. First, it accommodates the dynamic nature of the accumulations of genotype data during the genotyping process; some data need to be confirmed or replaced by repeat lab procedures. By using GenoDB, the raw genotype data can be imported easily and continuously and incorporated into the database during the genotyping process that may continue over an extended period of time in large projects. Second, almost all of the procedures are automatic, including autocomparison of the raw data read by different technicians from the same gel, autoadjustment among the allele fragment-size data from cross-runs or cross-platforms, autobinning of alleles, and autocompilation of genotype data for suitable programs to perform inheritance checkin pedigrees. Third, GenoDB provides functions to track electrophoresis gel files to locate gel or sample sources for any resultant genotype data, which is extremely helpful for double-checking consistency of raw and final data and for directing repeat experiments. In addition, the user-friendly graphic interface of GenoDB renders processing of large amounts of data much less labor-intensive. Furthermore, GenoDB has built-in mechanisms to detect some genotyping errors and to assess the quality of genotype data that then are summarized in the statistic reports automatically generated by GenoDB. The GenoDB can easily handle>500,000 genotype data entries, a number more than sufficient for typical whole-genome linkage studies. The modules and programs we developed for the GenoDB can be extended to other database platforms, such as Microsoft SQL server, if the capability to handle still greater quantities of genotype data simultaneously is desired.
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邓红文, Wei-Min Chen and Hong-Wen Deng, *
Genetic Epidemiology 21:53-67(2001),-0001,():
-1年11月30日
Transmission disequilibrium test (TDT) is a nuclear family-based analysis that can test linkage in the presence of association. It has gained extensive attention in theoretical investigation and in practical application; in both cases, the accuracy and generality of the power computation of the TDT are crucial. Despite extensive investigations, previous approaches for computing the statistical power of the TDT are neither accurate nor general. In this paper, we develop a general and highly accurate approach to analytically compute the power of the TDT. We compare the results from our approach with those from several other recent papers, all against the results obtained from computer simulations. We show that the results computed from our approach are more accurate than or at least the same as those from other approaches. More importantly, our approach can handle various situations, which include (1) families that consist of one or more children and that have any configuration of affected and nonaffected sibs; (2) families ascertained through the affection status of parent(s); (3) any mixed sample with different types of families in (1) and (2); (4) the marker locus is not a disease susceptibility locus; and (5) existence of allelic heterogeneity. We implement this approach in a user-friendly computer program: TDT Power Calculator. Its applications are demonstrated. The approach and the program developed here should be significant for theoreticians
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邓红文, Hong-Wen Deng, , Wei-Min Chen, and Robert R. Recker
Am. J. Hum. Genet. 66:1027-1045, 2000,-0001,():
-1年11月30日
It has recently been demonstrated that fine-scale mapping of a susceptibility locus for a complex disease can be accomplished on the basis of deviations from Hardy-Weinberg (HW) equilibrium at closely linked marker loci among affected individuals. We extend this theory to fine-scale localization of a quantitative-trait locus (QTL) from extreme individuals in populations, by means of HW and linkage-disequilibrium (LD) analyses. QTL mapping and/or linkage analyses can establish a large genomic region (~30cM) that contains a QTL. The QTL can be fine mapped by examination of the degree of deviation from HW and LD at a series of closely linked marker loci. The tests can be performed for samples of individuals belonging to either high or low percentiles of the phenotype distribution or for combined samples of these extreme individuals. The statistical properties (the power and the size) of the tests of this fine-mapping approach are investigated and are compared extensively, under various genetic models and parameters for the QTL and marker loci. On the basis of the results, a two-stage procedure that uses extreme samples and different tests (for HW and LD) is suggested for QTL fine mapping. This two-step procedure is economic and powerful and can accurately narrow a genomic region containing a QTL from~30-1cM, a range that renders physical mapping feasible for identification of the QTL. In addition, the relationship between parameterizations of complex diseases, by means of penetrance, and those of complex quantitative traits, by means of genotypic values, is outlined. This means that many statistical genetic methods developed for searching for susceptibility loci of complex diseases can be directly adopted and/or extended to QTL mapping for quantitative traits.
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邓红文, HONG-WEN DENG, , WEI-MIN CHEN, SUSAN RECKER, MARY RUTH STEGMAN, JIN-LONG LI, K. MICHAEL DAVIES, YAN ZHOU, HONGYI DENG, ROBERT HEANEY, and ROBERT R. RECKER
JOURNAL OF BONE AND MINERAL RESEARCH Volume 15, Number 7, 2000,-0001,():
-1年11月30日
Osteoporotic fractures (OFs) are a major public health problem. Direct evidence of the importance and, particularly, the magnitude of genetic determination of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwestern United States, we found significant genetic determination of CF. The prevalence (K) of CF is, respectively, 11.8% (6SE 0.7%) in 2471 proband women aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K0), the probability that a woman will suffer CF if her mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the probability that a sister of a proband woman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk l (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145;λo) for a woman with an affected mother and 1.885 (0.276;λs) for a woman with an affected sister. A l-value significantly greater than 1.0 indicates genetic determination of CF. The terms l0 and ls are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritability (0.254 [0.118]) for CF. These parameters were estimated by a maximum likelihood method that we developed, which provides a general tool for characterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for important covariates such as age, weight, etc.) than women with CF. (J Bone Miner Res 2000;15:1243-1252)
Colles', fracture,, heritability,, osteoporotic fracture,, genetic determination,, relative risk,, recurrence risk
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邓红文, Hong-Wen Deng
Hum Genet (1998) 103:576-585,-0001,():
-1年11月30日
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邓红文, Hong-Wen Deng
,-0001,():
-1年11月30日
Testing (over) dominance as the genetic cause of heterosis and estimating the (over)dominance coefficient (h) are related. Using simulations, we investigate the statistical properties of Mukai's approach, which is intended to estimate the average (h) of hi across loci by regression of outcrossed progeny on the sum of the two corresponding homozygous parents. A new approach for estimating h is also developed, utilizing data on families formed by multiple selfed genotypes from each outcrossed parent, thus not requiring constructing homozygotes. Assuming constant mutation effects, h can be estimated accurately by both approaches under dominance. When rare alleles have low frequencies at any polymorphic locus, Mukai's approach can estimate h accurately under over (under) dominance. Therefore, the (over) dominance hypothesis for heterosis can be tested by estimating h, under either dominance or overdominance at all genomic loci. However, this is invalid with more plausible mixed dominance and overdominance at different loci. Estimating the variance of hi across loci is also investigated. In self-compatible outcrossing populations with mutations of variable effects and lethals, our new approach is better than Mukai's, not only because of not requiring homozygotes but also because of the better statistical performance reflected by the smaller mean square errors of the estimates.
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【期刊论文】Inbreeding Depression and Inferred Deleterious-Mutation Parameters in Daphnia
邓红文, Hong-Wen Deng and Michael Lynch
,-0001,():
-1年11月30日
DENG and LYNCHre cently proposeda method for estimating deleterious genomic mutation parameters from changes in the mean and genetic variancoef fitness traits upon inbreeding in outcrossing populations. Such observations are readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. We observed a significant inbreeding depression and an increase of genetic variance for all traits analyzed. DENC and LYNCH's original proceduresw ere extended to estimate genomic mutation rate (U), mean dominance coefficient (A), mean selection coefficient (3), and scaled genomic mutational variance (Vm/Ve). On average, Û, h/ˆ, s/ˆand Vm/V (A indicates an estimate) are 0.74, 0.30, 0.14 and 4.6E-4, respectjvely. For the true values, the Û and h/∮are lower bounds, and s/ˆ and Vˆm/Ve upper bounds. The presenat Û, h/ˆ and Vˆm/Ve are in general concordance with earlier results. The discrepancy between the present Sand thfraot m mutation-accumulation experiments in Drosophila (~0.04) is discussed. It is shown that different reproductive modes do not affect gene frequency at mutationselection equilibrium if mutational effects on fitness are multiplicative and not completely recessive.
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