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Genes Underlying (gene + underlying)
Selected AbstractsNATURAL SELECTION ALONG AN ENVIRONMENTAL GRADIENT: A CLASSIC CLINE IN MOUSE PIGMENTATIONEVOLUTION, Issue 7 2008Lynne M. Mullen We revisited a classic study of morphological variation in the oldfield mouse (Peromyscus polionotus) to estimate the strength of selection acting on pigmentation patterns and to identify the underlying genes. We measured 215 specimens collected by Francis Sumner in the 1920s from eight populations across a 155-km, environmentally variable transect from the white sands of Florida's Gulf coast to the dark, loamy soil of southeastern Alabama. Like Sumner, we found significant variation among populations: mice inhabiting coastal sand dunes had larger feet, longer tails, and lighter pigmentation than inland populations. Most striking, all seven pigmentation traits examined showed a sharp decrease in reflectance about 55 km from the coast, with most of the phenotypic change occurring over less than 10 km. The largest change in soil reflectance occurred just south of this break in pigmentation. Geographic analysis of microsatellite markers shows little interpopulation differentiation, so the abrupt change in pigmentation is not associated with recent secondary contact or reduced gene flow between adjacent populations. Using these genetic data, we estimated that the strength of selection needed to maintain the observed distribution of pigment traits ranged from 0.0004 to 21%, depending on the trait and model used. We also examined changes in allele frequency of SNPs in two pigmentation genes, Mc1r and Agouti, and show that mutations in the cis -regulatory region of Agouti may contribute to this cline in pigmentation. The concordance between environmental variation and pigmentation in the face of high levels of interpopulation gene flow strongly implies that natural selection is maintaining a steep cline in pigmentation and the genes underlying it. [source] Common genetic influences underlie comorbidity of migraine and endometriosisGENETIC EPIDEMIOLOGY, Issue 2 2009Dale R. Nyholt Abstract We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12,2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (rG = 0.27, 95% CI: 0.06,0.47) and bivariate heritability (h2=0.17, 95% CI: 0.08,0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus,HEPATOLOGY, Issue 2 2008Giacomo Manenti The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis-susceptible C3H/He strain. Genome-wide linkage analysis using a 1536,single-nucleotide polymorphism array in a (C3H/He × BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score = 16.52 and accounted for 40% of the phenotypical variance. The BALB/c-derived allele at Hpcr3 reduced tumor-occupied area of the liver up to 25-fold, in a semidominant way. Additional minor loci were mapped to chromosomes 1, 10, and 18. A gene expression profile of normal adult mouse liver showed a significant association with susceptibility of BALB/c, C3H/He, and F1 mice to hepatocarcinogenesis and identified the genes expressed in the Hpcr3 locus region; moreover, this analysis implicated the E2F1 pathway in the modulation of the phenotype susceptibility to hepatocarcinogenesis. Conclusion: These findings, indicating the complex genetics of dominant resistance to hepatocarcinogenesis, represent a step toward the identification of the genes underlying this phenotype. (HEPATOLOGY 2008;48:617,623.) [source] QTL Analysis of Trabecular Bone in BXD F2 and RI Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Abbey L Bower Abstract A sample of 693 mice was used to identify regions of the mouse genome associated with trabecular bone architecture as measured using ,CT. QTLs for bone in the proximal tibial metaphysis were identified on several chromosomes indicating regions containing genes that regulate properties of trabecular bone. Introduction: Age-related osteoporosis is a condition of major concern because of the morbidity and mortality associated with osteoporotic fractures in humans. Osteoporosis is characterized by reduced bone density, strength, and altered trabecular architecture, all of which are quantitative traits resulting from the actions of many genes working in concert with each other and the environment over the lifespan. ,CT gives accurate measures of trabecular bone architecture providing phenotypic data related to bone volume and trabecular morphology. The primary objective of this research was to identify chromosomal regions called quantitative trait loci (QTLs) that contain genes influencing trabecular architecture as measured by ,CT. Materials and Methods: The study used crosses between C57BL/6J (B6) and DBA/2J (D2) as progenitor strains of a second filial (F2) generation (n = 141 males and 148 females) and 23 BXD recombinant inbred (RI) strains (n , 9 of each sex per strain). The proximal tibial metaphyses of the 200-day-old mice were analyzed by ,CT to assess phenotypic traits characterizing trabecular bone, including bone volume fraction, trabecular connectivity, and quantitative measures of trabecular orientation and anisotropy. Heritabilities were calculated and QTLs were identified using composite interval mapping. Results: A number of phenotypes were found to be highly heritable. Heritability values for measured phenotypes using RI strains ranged from 0.15 for degree of anisotropy in females to 0.51 for connectivity density in females and total volume in males. Significant and confirmed QTLs, with LOD scores ,4.3 in the F2 cohort and ,1.5 in the corresponding RI cohort were found on chromosomes 1 (43 cM), 5 (44 cM), 6 (20 cM), and 8 (49 cM). Other QTLs with LOD scores ranging from 2.8 to 6.9 in the F2 analyses were found on chromosomes 1, 5, 6, 8, 9, and 12. QTLs were identified using data sets comprised of both male and female quantitative traits, suggesting similar genetic action in both sexes, whereas others seemed to be associated exclusively with one sex or the other, suggesting the possibility of sex-dependent effects. Conclusions: Identification of the genes underlying these QTLs may lead to improvements in recognizing individuals most at risk for developing osteoporosis and in the design of new therapeutic interventions. [source] Effect of genotype and environment on branching in weedy green millet (Setaria viridis) and domesticated foxtail millet (Setaria italica) (Poaceae)MOLECULAR ECOLOGY, Issue 5 2006ANDREW N. DOUST Abstract Many domesticated crops are derived from species whose life history includes weedy characteristics, such as the ability to vary branching patterns in response to environmental conditions. However, domesticated crop plants are characterized by less variable plant architecture, as well as by a general reduction in vegetative branching compared to their progenitor species. Here we examine weedy green millet and its domesticate foxtail millet that differ in the number of tillers (basal branches) and axillary branches along each tiller. Branch number in F2:3 progeny of a cross between the two species varies with genotype, planting density, and other environmental variables, with significant genotype,environment interactions (GEI). This is shown by a complex pattern of reaction norms and by variation in the pattern of significant quantitative trait loci (QTL) amongst trials. Individual and joint analyses of high and low density trials indicate that most QTL have significant GEI. Dominance and epistasis also explain some variation in branching. Likely candidate genes underlying the QTL (based on map position and phenotypic effect) include teosinte branched1 and barren stalk1. Phytochrome B, which has been found to affect response to shading in other plants, explains little or no variation. Much variation in branching is explained by QTL that do not have obvious candidate genes from maize or rice. [source] Genetic studies of common types of obesity: a critique of the current use of phenotypesOBESITY REVIEWS, Issue 8 2010M. J. Müller Summary Recent research into the genetic basis of obesity has focused upon the study of candidate genes, both functional and positional, of genes underlying weight-related Mendelian disorders and of susceptibility loci identified in genome-wide association studies. Three large genome-wide association studies on obesity, together involving more than 150 000 individuals, were published in Nature Genetics last year. The results suggested the involvement of a large number of genetic variants in disease susceptibility. Most genetic effects upon body weight are likely to become obscured by the use of inappropriate phenotypes. In particular, clinical categories such as the body mass index and Metabolic Syndrome do not provide sufficient etiological information for them to be used sensibly in genetic studies on obesity or obesity-related disease. Alleviation of this situation will not come from new genomic research tools, sophisticated statistical algorithms or ever larger sample sizes. Instead, the above notions argue in favour of so-called ,deep phenotyping'. [source] Analysis of candidate genes underlying two epistatic quantitative trait loci on SSC12 affecting litter size in pigANIMAL GENETICS, Issue 1 2010A. Fernández-Rodríguez Summary The previous results from a genome scan for total number of piglets born and number of piglets born alive in a F2 Iberian by Meishan intercross showed several single and epistatic QTL. One of the most interesting results was obtained for SSC12, where two QTL affecting both traits showed epistatic interaction. In this study, we proposed two genes (SLC9A3R1 and NOS2) as biological and potentially positional candidates underlying these QTL. Both cDNAs were characterized and 23 polymorphisms were detected. A chromosome scan was conducted with 12 markers, plus one SNP in SLC9A3R1 and one in NOS2, covering 110 cM of SSC12. The epistatic QTL (QTL1 at 15 cM and QTL2 at 97 cM) were confirmed, and SLC9A3R1 and NOS2 were mapped around the QTL1 and QTL2 regions respectively. Several SNPs in both genes were tested with standard animal model and marker assisted association tests. The most significant results were obtained with the NOS2 haplotype defined by one missense SNP c.2192C > T (Val to Ala) and a 15 bp duplication at the 3,UTR. This duplication seems to include AU-rich elements, and could be a target site for miRNA, therefore there are statistical and biological indications to consider this haplotype as the potential causal mutation underlying QTL2. SLC9A3R1 results were not conclusive. Although the interaction between the SNPs was not significant, we cannot reject the possibility of interaction of the NOS2 haplotype with other polymorphisms closely linked to the SL9A3R1 SNPs analysed. [source] 2243: Update on inherited ocular developmental diseaseACTA OPHTHALMOLOGICA, Issue 2010GCM BLACK Purpose To provide an overview of progress in understanding of the genetics of developmental ocular disease. Methods A systematic review, including case presentations, to illustrate insights into genes underlying developmental ocular disorders: Results Studies suggest that, in developed countries, between a third and a half of the diagnoses underlying childhood blind or partial-sighted registration are genetic while a number of other ,non-genetic' conditions also have a substantial genetic contribution. Such a figure is likely to be an underestimate. Although most of these conditions are rare, many of the issues regarding diagnosis and counselling apply to the group as a whole and it is therefore possible to consider a common approach to many aspects of their clinical management. An important challenge, for example, is to improve genetic counselling for patients affected by, and at risk of, disorders that may be caused by a genetic change in one of many possible genes, which typifies many inherited conditions associated with blindness (developmental ocular disorders, early-onset retinal dystrophies, congenital cataract). Most diagnostic genetic testing currently being undertaken focuses on single genes; this will be illustrated for ocular conditions such as retinoblastoma, Norrie disease and microphthalmia. However future prospects will focus upon use of new higher throughput technologies (e.g Microarray technologies). Conclusion The recent identification of genes underlying, for example, anophthalmia/microphthalmia spectrum (e.g. VSX2, SOX2, BCOR), anterior segment dysgenesis (e.g. PITX2, FOXC1, FOXE3) and early,onset retinal disorders (e.g. ADVIRC, RPE65) has shed light on the pathways and processes underlying a range of the biological processes underlying ocular development. [source] Glyc-O-genetics of Walker,Warburg syndromeCLINICAL GENETICS, Issue 4 2005J Van Reeuwijk Walker,Warburg syndrome (WWS) is the most severe of a group of multiple congenital anomaly disorders known as the cobblestone lissencephalies. These are characterized by congenital muscular dystrophy in conjunction with severe brain malformation and ocular abnormalities. In the last 3 years, important progress has been made towards the elucidation of the genetic causes of these disorders. Mutations in three genes, POMT1, fukutin and FKRP, have been described for WWS, which together account for approximately 20% of patients with Walker,Warburg. It has become evident that some of the underlying genes may cause a broad spectrum of phenotypes, ranging from limb girdle muscular dystrophy type 2I to WWS. In some cases, a genotype,phenotype correlation can be recognized. In line with the known or proposed functions of the resolved genes, all patients with cobblestone lissencephaly show defects in the O-linked glycosylation of the glycoprotein ,-dystroglycan. Perhaps, the missing genes underlying the remainder of the unexplained WWS patients have also to be sought in the pathways involved in O-linked protein glycosylation. [source] | |||||||||||||