病理性近视的家系研究

为了探讨我国病理性近视的遗传模式,对90个病理性近视大家系进行了分离分析。简单分离分析采用先验法和SEGRAN-B软件,进行拟合优度卡方检验,比较实际分离比与理论分离比的符合程度;复合分离分析运用SAGE-REGD软件进行孟德尔遗传模型(主基因、显性、隐性、共显性)和非孟德尔遗传模型(非传递、环境、一般)的拟合。结果显示,婚配类型为A*N的家系符合常染色体显性遗传,散发概率为13．8％,婚配类型为N*N的家系符合常染色体隐性遗传,散发概率为16．3％,但常染色体显性遗传不能除外,复合分离分析接受孟德尔遗传的显性、隐性、共显性和主基因模型,共显性模型的可能性最大,基因频率为0．21442999。因此,我国病理性近视存在常染色体显性和隐性遗传模式,并有一定比例的散发病例,具有遗传异质性。     

Heterogeneity of genetic control of blood pressure in ethnically different populations.

We review the literature on statistical genetic analyses of blood pressure in samples from various ethnic backgrounds using different statistical methods and packages. We then provide the results of a complex segregation analysis performed on familial data on systolic and diastolic blood pressure in 2 ethnically different populations, Chuvashans and Turkmenians. Two types of major gene models were tested in the segregation analysis: Model type 1 tests for a Mendelian mode of transmission and estimates genotype-specific averages regardless of age and sex effect, and model type 2 estimates age and sex effects on each of 3 genotypes within the putative major genotype. In both total samples, by both types of segregation analysis, familial aggregation of both systolic and diastolic blood pressure was inconsistent with the Mendelian mode of inheritance. In the next step of analysis the pedigrees in both samples were sorted into 2 groups on the basis of 2 likelihoods as obtained under Mendelian and nontransmission models for each entire sample. This procedure resulted in the appearance of 2 subsamples (large and small) in each ethnic sample. The segregation analysis that was carried out then on the larger subsample provided consistent evidence to support the major gene effect on systolic and diastolic blood pressure in 2 ethnic groups. Interestingly, model type 2 showed that in both ethnically different large subsamples, for each sex the genotype predisposing to a larger mean value of systolic (or diastolic) blood pressure also displayed the highest rate of blood pressure increase with age. We discuss in detail possible sources of heterogeneity in familial transmission of blood pressure observed in our 2 samples, and we suggest a method to improve the analysis of heterogeneity for trait inheritance.     

Inheritance of the general shell color in the scallop Argopecten purpuratus (Bivalvia: Pectinidae)

Although some external coloration and pigmentation patterns in molluscan shells may be attributable to environmental factors, most variation in these phenotypic characters depends on uncomplicated genetic mechanisms. Genetic research on inheritance of color variations in the north-Chilean scallop (Argopecten purpuratus) has now been expanded to analyze color segregation in juvenile scallops produced under controlled conditions employing self- and cross-fertilization. Calculations from the results were used for comparison with different numerical models based on Mendelian inheritance, and results were also obtained on the inheritance of a dorsoventral white line often observed on the left (upper) valve in this species. The results confirmed the hereditary basis for color variation in the shell of this scallop, suggesting a simple, dominant model of epistasis to explain the distribution of the different color variants observed (purple, brown, orange, yellow, and white). The presence of the white line may be controlled by a recessive allele with simple Mendelian traits on a locus distinct from those that control color variation.     

Segregation Analysis on Genetic System of Quantitative Traits in Plants

Based on the traditional polygene inheritance model of quantitative traits,the author suggests the major gene and polygene mixed inheritance model.The model was considered as a general one,while the pure major gene and pure polygene inheritance model was a specific case of the general model.Based on the proposed theory,the author established the segregation analysis procedure to study the genetic system of quantitative traits of plants.At present,this procedure can be used to evaluate the genetic effect of individual major genes (up to two to three major genes),the collective genetic effect of polygene,and their heritability value.This paper introduces how to establish the procedure,its main achievements,and its applications.An example is given to illustrate the steps,methods,and effectiveness of the procedure.     

Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a “Mendelian segregation” model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance.     

Segregation Analysis on Genetic System of Quantitative Traits in Plants

Based on the traditional polygene inheritance model of quantitative traits, the author suggests the major gene and polygene mixed inheritance model. The model was considered as a general one, while the pure major gene and pure polygene inheritance model was a specific case of the general model. Based on the proposed theory, the author established the segregation analysis procedure to study the genetic system of quantitative traits of plants. At present, this procedure can be used to evaluate the genetic effect of individual major genes (up to two to three major genes), the collective genetic effect of polygene, and their heritability value. This paper introduces how to establish the procedure, its main achievements, and its applications. An example is given to illustrate the steps, methods, and effectiveness of the procedure. Translated from Hereditas, 2005, 27(1) (in Chinese)     

Inheritance of RAPD molecular makers in lake trout Salvelinus namaycush

Inheritance patterns of randomly amplified polymorphic DNA (RAPD) phenotypes were tested in 13 full-sib families of lake trout Salvelinus namaycush . Single-pair matings of parents with known phenotypes were made, and up to 20 progeny of each mating were used to test inheritance patterns. Seven RAPD primers amplified 13 polymorphic bands. With the exception of one family, expected segregation ratios for dominant Mendelian genetic traits were observed. Our results support previously reported findings that RAPD markers can be considered Mendelian traits and therefore could be used for analysis of genetic population structure.     

Whole-genome linkage disequilibrium screening for complex traits in horses

The identification of candidate genes for significant traits is crucial. In this study, we developed and tested effective and systematic methods based on linkage disequilibrium (LD) for the identification of candidate regions for genes with Mendelian inheritance and those associated with complex traits. Our approach entailed the combination of primary screening using pooled DNA samples based on ΔTAC, secondary screening using an individual typing method and tertiary screening using a permutation test based on the differences in the haplotype frequency between two neighbouring microsatellites. This series of methods was evaluated using horse coat colour traits (chestnut/non-chestnut) as a simple Mendelian inheritance model. In addition, the methods were evaluated using a complex trait model constructed by mixing samples from chestnut and non-chestnut horses. Using both models, the methods could detect the expected regions for the horse coat colour trait. The results revealed that LD extends up to several centimorgans in horses, indicating that whole-genome LD screening in horses could be performed systematically and efficiently by combining the above-mentioned methods. Since genetic maps based on microsatellites have been constructed for many other species, the approaches present here could have wide applicability.     

植物数量性状遗传体系的分离分析方法研究

在传统的数量性状多基因遗传模型基础上提出主基因-多基因遗传模型具普遍性,纯主基因或纯多基因遗传模型只是其特例。由此初步建立了植物数量性状遗传体系分离分析方法。目前该方法可以检验2～3个主基因的个别遗传效应、多基因整体的遗传效应和两者的遗传率。本文介绍这种分离分析方法的研究经过、主要进展及应用效果,并以实例说明其分析步骤、方法和效果。     

Complex segregation analysis of nonsyndromic cleft lip and palate.

This study was undertaken to examine the inheritance pattern of nonsyndromic cleft lip with or without cleft palate (CL/P). Complex segregation analysis using the unified model as in POINTER and the regressive model as in REGD programs were applied to analyze a midwestern U.S. Caucasian population of 79 families ascertained through a proband with CL/F. In REGD, the dominant or codominant Mendelian major locus models of inheritance were the most parsimonious fit. In POINTER, besides the Mendelian major locus model, the multifactorial threshold (MF/T) model and the mixed model were also consistent with the observed data. However, the high heritability parameter of .93 (SD .063) in the MF/T model suggests that any random exogenous factors are unlikely to be the underlying mechanisms, and the mixed model indicates that this high heritability is accounted for by a major dominant locus component. These findings indicate that the best explanation for the etiology of CL/P in this study population is a putative major locus associated with markedly decreased penetrance. Molecular studies may provide further insight into the genetic mechanism underlying CL/P.     

利用DH或RIL群体检测QTL体系并估计其遗传效应

利用ＤＨ和ＲＩＫＬ群体并结合重复内分组随机区组设计对和物产量等遗传率较低的数量性状进行分离分析可提高遗传分析的精度。根据混合分布理论菜了利用ＤＨ或ＲＩＬ群体重复实验数据鉴定数量性状混合遗传模型的分离分析法,特别是２对链锁主基因＋多基因模型。该方法可鉴定数量性状的遗传模型和主基因的作用方式,估计主基因、多基因的遗传疚和遗传方差,在两主基因存在连锁可可估计其重组率。下面通过应用举例说明该方法。     

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P₁ and P₂), F₁, F₂, and both backcross generations (B₁ and B₂) derived from crossing the F₁ to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes. Received: 18 August 2000 / Accepted: 9 March 2001     

Beyond Mendel: an evolving view of human genetic disease transmission

Methodological and conceptual advances in human genetics have led to the identification of an impressive number of human disease genes. This wealth of information has also revealed that the traditional distinction between Mendelian and complex disorders might sometimes be blurred. Genetic and mutational data on an increasing number of disorders have illustrated how phenotypic effects can result from the combined action of alleles in many genes. In this review, we discuss how an improved understanding of the genetic basis of multilocus inheritance is catalysing the transition from a segmented view of human genetic disease to a conceptual continuum between Mendelian and complex traits.     

Segregation distortion for seed testa color in Mungbean (Vigna radiata L. Wilcek)

Genetic segregation experiments with plant species are commonly used for understanding the inheritance of traits. A basic assumption in these experiments is that each gamete developed from megasporogenesis has an equal chance of fusing with a gamete developed from microsporogenesis, and every zygote formed has an equal chance of survival. If gametic and/or zygotic selection occurs whereby certain gametes or zygotic combinations have a reduced chance of survival, progeny distributions are skewed and are said to exhibit segregation distortion. In this study, inheritance data are presented for the trait seed testa color segregating in large populations (more than 200 individuals) derived from closely related mungbean (Vigna radiata L. Wilcek) taxa. Segregation ratios suggested complex inheritance, including dominant and recessive epistasis. However, this genetic model was rejected in favor of a single-gene model based on evidence of segregation distortion provided by molecular marker data. The segregation distortion occurred after each generation of self-pollination from F1 thru F7 resulting in F7 phenotypic frequencies of 151:56 instead of the expected 103.5:103.5. This study highlights the value of molecular markers for understanding the inheritance of a simply inherited trait influenced by segregation distortion.     

Mode of inheritance of hand osteoarthritis in ethnically homogeneous pedigrees

The aim of the present study was to investigate the extent and mode of inheritance of hand osteoarthritis (OA) using a large sample of ethnically homogeneous pedigrees. Two types of segregation analysis (SA) models were examined. Type I models used the data adjusted for potential significant covariates, particularly age and sex, prior to genetic analysis. Type 11 models incorporated effects of the potential covariates into major gene penetrance functions, permitting an account of the genotype covariate-specific effect on study variables. The results of this study strongly supported the hypothesis of a major gene effect and additional multifactorial component. The best-fitting model was the Mendelian one with an additive type of inheritance. The estimates obtained using the standard three-factor variance decomposition analysis suggest that age (72.8%) and major gene (14.5%) are the main sources of interindividual differences in the development of hand OA. The contribution of the putative major gene on age- and sex-adjusted OA phenotype variation was 55% in the present study.     

Inheritance of the Waist‐to‐Hip Ratio in the National Heart,Lung, and Blood Institute Family Heart Study

Objective: Considering that waist‐to‐hip ratio (WHR) is a simple anthropometric measure of obesity and is a better predictor of coronary heart disease than body mass index (BMI), the genetic underpinnings of WHR are of interest. The inheritance pattern of WHR, before and after adjustment for BMI (WHR‐BMI), was investigated in 2713 individuals from 1038 nuclear families in the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI‐FHS). Research Methods and Procedures: Waist and hip measurements were taken twice, and the means of the measurements were used to calculate the WHR. Adjustments for age were carried out separately by sex, using stepwise multiple regression procedures for WHR and WHR‐BMI phenotypes. Segregation analysis was applied using the unified model as implemented in the computer program POINTER. Results: For age‐adjusted WHR, the segregation results suggested an additive major gene that accounts for 35% of the phenotypic variance, and approximately 30% of the sample are homozygous for the “high” genotype. The results for age‐ and BMI‐adjusted WHR were also compatible with a major gene; however, the multifactorial model provided the most parsimonious fit to the data. Discussion: Although the genetic mechanisms for several obesity traits have been studied, tests of Mendelian segregation on this simple anthropometric measure (WHR) have not been reported previously. This study provides evidence for the presence of a major gene for age‐adjusted WHR, suggesting that it is an appropriate trait for further genetic analysis, especially because it has strong predictive value and probably relates biologically to cardiovascular risk.     

Evidence of a major gene from Bayesian segregation analyses of liability to osteochondral diseases in pigs

Bayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384-37.81), compared to the polygenic variance (sigmau2). Consequently, heritabilities for a mixed inheritance (range 0.65-0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38-0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on sigmau2, showed significant improvement in marginal distributions and accuracy of parameters. MITM with a "reduced polygenic model" for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an "individual polygenic model." In all cases, "shrinkage estimators" for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans.     

SASQuant: a SAS software program to estimate genetic effects and heritabilities of quantitative traits in populations consisting of 6 related generations

Plant breeders are interested in the analysis of phenotypic data to measure genetic effects and heritability of quantitative traits and predict gain from selection. Measurement of phenotypic values of 6 related generations (parents, F(1), F(2), and backcrosses) allows for the simultaneous analysis of both Mendelian and quantitative traits. In 1997, Liu et al. released a SAS software based program (SASGENE) for the analysis of inheritance and linkage of qualitative traits. We have developed a new program (SASQuant) that estimates gene effects (Hayman's model), genetic variances, heritability, predicted gain from selection (Wright's and Warner's models), and number of effective factors (Wright's, Mather's, and Lande's models). SASQuant makes use of traditional genetic models and allows for their easy application to complex data sets. SASQuant is freely available and is intended for scientists studying quantitative traits in plant populations.     

Complex segregation analysis reveals a multigene model for lung cancer

Lung cancer risk is largely attributed to tobacco exposure, but genetic predisposition also plays an etiologic role. Several studies have investigated the involvement of genetic predisposition in lung cancer aggregation in affected families, although with inconsistent results. Some studies have provided evidence for Mendelian inheritance, whereas others have suggested that environmental models are most appropriate for lung cancer aggregation in families. To examine the genetic basis of lung cancer, we performed segregation analysis on 14,378 individuals from 1,561 lung cancer case families, allowing for the effects of smoking, sex, and age. Both a Mendelian decreasing model and a Mendelian codominant model were found to be the best fitting models for susceptibility. However, when we modeled age-of-onset, all Mendelian models and the environmental model were rejected suggesting that multiple genetic factors (possibly multiple genetic loci and interactions) contribute to the age-of-onset of lung cancer. The results provide evidence that multiple genetic factors contribute to lung cancer and may act as a guide in further studies to localize susceptibility genes in lung cancer.     

Segregation analysis of alcoholism in families ascertained through a pair of male alcoholics.

To determine the nature of the genetic component controlling liability to alcoholism, complex segregation analysis was performed on 35 multigenerational families each ascertained through a pair of male alcoholics. The results suggest that liability to alcoholism is, in part, controlled by a major effect with or without additional multifactorial effects. Mendelian transmission of this major effect was rejected, as was the hypothesis that the major effect is due to a single major locus. Absence of this major effect, leaving only multifactorial effects, was also rejected. Some sources for the non-Mendelian character of the major effect are suggested, such as a combination of two or more Mendelian loci, the presence of phenocopies, sex-dependent differences in the underlying liability model, or heterogeneity in the alcoholism phenotype. Evidence for and against each is discussed.