Variants in EMX2 and PTEN do not contribute to risk of endometriosis

Endometriosis has a genetic component, and significant linkage has been found to a region on chromosome 10q. Two candidate genes, EMX2 and PTEN, implicated in both endometriosis and endometrial cancer, lie on chromosome 10q. We hypothesized that variation in EMX2 and/or PTEN could contribute to the risk of endometriosis and may account for some of the linkage signal on 10q. We genotyped single nucleotide polymorphisms (SNPs) in a case-control design to evaluate association between endometriosis and common variations in these two genes. The genotyping and statistical analysis were based on samples collected from Australian volunteers. The cases were 768 unrelated women with surgically confirmed endometriosis selected from affected sister pair (ASP) families participating in the Australian Genes behind Endometriosis Study. The controls were 768 female participants in twin studies who, based on screening questions, did not have a diagnosis of endometriosis. Genotypes of 22 SNPs in the EMX2 gene and 15 SNPs in the PTEN gene were the main outcome measures. Statistical analysis provided measures of linkage disequilibrium and association. Permutation testing showed no globally significant association between any SNPs or haplotypes and endometriosis for either gene. It is unlikely that the EMX2 or PTEN gene variants investigated contribute to risk for initiation and/or development of endometriosis.

ssSNPer: identifying statistically similar SNPs to aid interpretation of genetic association studies

ssSNPer is a novel user-friendly web interface that provides easy determination of the number and location of untested HapMap SNPs, in the region surrounding a tested HapMap SNP, which are statistically similar and would thus produce comparable and perhaps more significant association results. Identification of ssSNPs can have crucial implications for the interpretation of the initial association results and the design of follow-up studies. AVAILABILITY: http://fraser.qimr.edu.au/general/daleN/ssSNPer/

Genetic diversity of Atlantic salmon (Salmo salar) and European whitefish (Coregonus lavaretus) in the Baltic Sea

We described the patterns and extent of microsatellite DNA variation in historical and present-day Atlantic salmon (Salmo salar L.) stocks in the Baltic Sea and neighbouring areas, and in European whitefish (Coregonus lavaretus) ecotypes, populations and run-timing types in Finland. Moreover, the amount and pattern of genetic diversity in historical salmon populations before human impact were described, and the proportion of diversity maintained in the present hatchery stocks evaluated. Salmon populations in the Baltic Sea were, on average, significantly less variable than eastern Atlantic populations, and the diversity of landlocked populations (Lakes Vänern, Saimaa, Onega and Ladoga) was in turn significantly lower than that of anadromous salmon populations in the Baltic Sea populations. Within the Baltic Sea, the anadromous populations of Atlantic salmon formed three clear groups, corresponding to the northern (Gulf of Bothnia), eastern (Gulf of Finland and eastern Baltic Main Basin) and southern (western Baltic Main Basin) regions. Based on microsatellite data, three salmon population groups in the Baltic Sea were considered potentially different colonization lineages. In short- and long-term breeding programmes of Atlantic salmon, the average observed rate of loss of alleles was 4.9% and 2.0% per generation and the average rate of loss of heterozygosity was 1.4% and 1% per generation, respectively. When comparing the genetic parameters of stocks before and after hatchery breeding of several successive generations (Rivers Iijoki and Oulujoki), statistically significant changes in allele frequencies were common, while large wild stock in the Teno River has remained temporally very stable over 56 years. Despite the observed losses of genetic diversity in broodstock breeding, a large proportion of the genetic resources of the extirpated stocks are still conserved in the broodstocks. Genetic differentiation among European whitefish ecotypes was generally low, thus giving support to the hypothesis of one native European whitefish species in Fennoscandia. Among the ecotypes, the northern, large sparsely rakered, bottom-dwelling whitefish was the most unique. The known genetic differences in quantitative traits have thus either developed independently of potential phylogenetic lineages, or the lineages have mixed and the quantitative traits of the ecotypes, like gill-raker number, have later changed according to environment and selection pressures. Overall, genetic distances between the anadromous whitefish populations along the Finnish coast, especially in the Bothnian Bay area, were small. Wild whitefish populations studied had slightly higher allelic diversity than hatchery-reared populations in corresponding rivers.

Male traits and herd reproductive capability in tropical beef cattle. 2. Genetic parameters of bull traits

A total of 4063 young bulls of two tropical genotypes (1639 Brahman and 2424 Tropical Composite) raised in northern Australia were evaluated for a comprehensive range of production and reproduction traits up to 24 months of age. Prior to weaning, peripheral blood concentrations of luteinising hormone (LH) and inhibin were measured at 4 months of age. At weaning (6 months) blood insulin-like growth factor-1 (IGF-I) and flight time were recorded. Body composition traits of fat depth and eye-muscle area were determined by ultrasonography at 15 months of age when additional measurements of liveweight, hip height and body condition score were recorded. Bull breeding soundness was evaluated at similar to 12, 18 and 24 months of age when measurements of scrotal circumference, sheath score, semen mass activity, progressive motility of individual sperm and percent morphologically normal sperm were recorded. Magnitude of heritability and genetic correlations changed across time for some traits. Heritability of LH, inhibin, IGF-I and of 18-month scrotal circumference, mass activity, progressive motility and percent normal sperm was 0.31, 0.74, 0.44, 0.75, 0.24, 0.15 and 0.25, respectively, for Brahmans and 0.48, 0.72, 0.36, 0.43, 0.13, 0.15 and 0.20, respectively, for Tropical Composites. Inhibin and IGF-I had moderate genetic association with percent normal sperm at 24 months in Brahmans but low to negligible associations in Tropical Composites. Body condition score in Brahmans and sperm motility (mass and individual) traits in both genotypes had moderate to strong genetic correlation with percent normal sperm and may prove useful candidates for indirect selection. There is scope to increase scrotal circumference by selection and this will be associated with favourable correlated responses of improved semen quality in both genotypes. The lack of genetic antagonism among bull traits indicates that selection for improved semen quality will not adversely affect other production traits.

Predicting Additive and Non-additive Genetic Effects from Trials Where Traits Are Affected by Interplot Competition

There are two key types of selection in a plant breeding program, namely selection of hybrids for potential commercial use and the selection of parents for use in future breeding. Oakey et al. (in Theoretical and Applied Genetics 113, 809-819, 2006) showed how both of these aims could be achieved using pedigree information in a mixed model analysis in order to partition genetic effects into additive and non-additive effects. Their approach was developed for field trial data subject to spatial variation. In this paper we extend the approach for data from trials subject to interplot competition. We show how the approach may be used to obtain predictions of pure stand additive and non-additive effects. We develop the methodology in the context of a single field trial using an example from an Australian sorghum breeding program.

Trait components provide tools to dissect the genetic susceptibility of migraine

The commonly used "end diagnosis" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society (IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components--individual clinical symptoms of migraine--to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 (highest LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia (10q22) and aggravation by physical exercise (12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society (IHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2)=0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine.

Genetic and environmental influences on migraine: a twin study across six countries

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

GENEHUNTER: your 'one-stop shop' for statistical genetic analysis?

The past decade has brought a proliferation of statistical genetic (linkage) analysis techniques, incorporating new methodology and/or improvement of existing methodology in gene mapping, specifically targeted towards the localization of genes underlying complex disorders. Most of these techniques have been implemented in user-friendly programs and made freely available to the genetics community. Although certain packages may be more 'popular' than others, a common question asked by genetic researchers is 'which program is best for me?'. To help researchers answer this question, the following software review aims to summarize the main advantages and disadvantages of the popular GENEHUNTER package.

Evidence for an X-linked genetic component in familial typical migraine

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.

Genetic control of nodal root angle in sorghum and its implications on water extraction

Genotypic variability in root system architecture has been associated with root angle of seedlings and water extraction patterns of mature plants in a range of crops. The potential inclusion of root angle as a selection criterion in a sorghum breeding program requires (1) availability of an efficient screening method, (2) presence of genotypic variation with high heritability, and (3) an association with water extraction pattern. The aim of this study was to determine the feasibility for inclusion of nodal root angle as a selection criterion in sorghum breeding programs. A high-throughput phenotypic screen for nodal root angle in young sorghum plants has recently been developed and has been used successfully to identify significant variation in nodal root angle across a diverse range of inbred lines and a mapping population. In both cases, heritabilities for nodal root angle were high. No association between nodal root angle and plant size was detected. This implies that parental inbred lines could potentially be used to asses nodal root angle of their hybrids, although such predictability is compromised by significant interactions. To study effects of nodal root angle on water extraction patterns of mature plants, four inbred lines with contrasting nodal root angle at seedling stage were grown until at least anthesis in large rhizotrons. A consistent trend was observed that nodal root angle may affect the spatial distribution of root mass of mature plants and hence their ability to extract soil water, although genotypic differences were not significant. The potential implications of this for specific adaptation to drought stress are discussed. Results suggest that nodal root angle of young plants can be a useful selection criterion for specific drought adaptation, and could potentially be used in molecular breeding programs if QTLs for root angle can be identified. (C) 2012 Elsevier B.V. All rights reserved.