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The genetic basis of prezygotic reproductive isolation between Drosophila santomea and D. yakuba due to mating preference.

Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila santomea and D. yakuba. We mapped at least three QTL affecting discrimination of D. santomea females against D. yakuba males: one X-linked and one autosomal QTL affected the likelihood of copulation, and a second X chromosome QTL affected copulation latency. Three autosomal QTL also affected mating success of D. yakuba males with D. santomea. No epistasis was detected between QTL affecting sexual isolation. The QTL do not overlap between males and females and are not disproportionately concentrated on the X chromosome. There was some overlap in map locations of QTL affecting sexual isolation between D. santomea and D. yakuba with QTL affecting sexual isolation between D. simulans and D. mauritiana and with QTL affecting differences in pigmentation between D. santomea and D. yakuba. Future high-resolution mapping and, ultimately, positional cloning, will reveal whether these traits do indeed have a common genetic basis.

Animals↗

Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1.

A genetic map for rat chromosome 1 was constructed using 66 microsatellite markers typed on either or both of two populations derived from inbred Dahl salt-sensitive (S) rats: F2(LEW x S) n = 151, and F2(WKY x S) n = 159. These populations had been raised on a high salt (8% NaCl) diet. Systolic blood pressure and heart weight were found to be genetically linked to two separate regions on rat chromosome 1 in the F2(LEW x S) population. One region was centered around the anonymous SA locus and accounted for 24 mmHg of blood pressure. The other region was 55 cM from the SA locus centered around a cluster of cytochromes P450 loci, and accounted for 30 mmHg of blood pressure. Since blood pressure and heart weight were highly correlated these same regions were also linked to heart weight. These results were cross-specific as linkage of these chromosome 1 regions to blood pressure and heart weight was not observed in several other F2 populations derived by crossing S and other normotensive control strains. This is presumably due to different alleles and/or different genetic backgrounds in the various populations. The SA region of chromosome 1 was found to influence body weight in F2(LEW x S) rats. Combining the present data with our previously published data on the F2(LEW x S) population showed that four separate quantitative trait loci with additive effects accounted for 106 mmHg and 38% of the total variance of blood pressure and for 506 mg and 34% of the total variance of heart wt.

Animals↗

Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster.

The nature of genetic variation for Drosophila longevity in a population of recombinant inbred lines was investigated by estimating quantitative genetic parameters and mapping quantitative trait loci (QTL) for adult life span in five environments: standard culture conditions, high and low temperature, and heat-shock and starvation stress. There was highly significant genetic variation for life span within each sex and environment. In the analysis of variance of life span pooled over sexes and environments, however, the significant genetic variation appeared in the genotype x sex and genotype x environment interaction terms. The genetic correlation of longevity across the sexes and environments was not significantly different from zero in these lines. We estimated map positions and effects of QTL affecting life span by linkage to highly polymorphic roo transposable element markers, using a multiple-trait composite interval mapping procedure. A minimum of 17 QTL were detected; all were sex and/or environment-specific. Ten of the QTL had sexually antagonistic or antagonistic pleiotropic effects in different environments. These data provide support for the pleiotropy theory of senescence and the hypothesis that variation for longevity might be maintained by opposing selection pressures in males and females and variable environments. Further work is necessary to assess the generality of these results, using different strains, to determine heterozygous effects and to map the life span QTL to the level of genetic loci.

Animals↗

A genetic linkage map of Pacific white shrimp (Litopenaeus vannamei): sex-linked microsatellite markers and high recombination rates.

Pacific white shrimp (Litopenaeus vannamei) is the leading species farmed in the Western Hemisphere and an economically important aquaculture species in China. In this project, a genetic linkage map was constructed using amplified fragment length polymorphism (AFLP) and microsatellite markers. One hundred and eight select AFLP primer combinations and 30 polymorphic microsatellite markers produced 2071 markers that were polymorphic in either of the parents and segregated in the progeny. Of these segregating markers, 319 were mapped to 45 linkage groups of the female framework map, covering a total of 4134.4 cM; and 267 markers were assigned to 45 linkage groups of the male map, covering a total of 3220.9 cM. High recombination rates were found in both parental maps. A sex-linked microsatellite marker was mapped on the female map with 6.6 cM to sex and a LOD of 17.8, two other microsatellite markers were also linked with both 8.6 cM to sex and LOD score of 14.3 and 16.4. The genetic maps presented here will serve as a basis for the construction of a high-resolution genetic map, quantitative trait loci (QTLs) detection, marker-assisted selection (MAS) and comparative genome mapping.

Animals↗

Complex trait analysis of the hippocampus: mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice.

Notable differences in hippocampal structure are associated with intriguing differences in development and behavioral capabilities. We explored genetic and environmental factors that modulate hippocampal size, structure, and cell number using sets of C57BL/6J (B6) and DBA/2J (D2) mice; their F1 and F2 intercrosses (n = 180); and 35 lines of BXD recombinant inbred (RI) strains. Hippocampal weights of the parental strains differ by 20%. Estimates of granule cell number also differ by approximately 20%. Hippocampal weights of RI strains range from 21 to 31 mg, and those of individual F2 mice range from 23 to 36 mg (bilateral weights). Volume and granule cell number are well correlated (r = 0.7-0.8). Significant variation is associated with differences in age and sex. The hippocampus increases in weight by 0.24 mg per month, and those of males are 0.55 mg heavier (bilateral) than those of females. Heritability of variation is approximately 50%, and half of this genetic variation is generated by two quantitative trait loci that map to chromosome 1 (Hipp1a: genome-wide p < 0.005, between 65 and 100 cM) and to chromosome 5 (Hipp5a, p < 0.05, between 15 and 40 cM). These are among the first gene loci known to produce normal variation in forebrain structure. Hipp1a and Hipp5a individually modulate hippocampal weight by 1.0-2.0 mg, an effect size greater than that generated by age or sex. The Hipp gene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for the Hipp loci include Rxrg and Fgfr3.

Aging↗

Linkage analysis of quantitative trait loci in multiple line crosses.

Simple line crosses, for example, backcross and F2, are commonly used in mapping quantitative trait loci (QTL). However, these simple crosses are rarely used alone in commercial plant breeding; rather, crosses involving multiple inbred lines or several simple crosses but connected by shared inbred lines may be common in plant breeding. Mapping QTL using crosses of multiple lines is more relevant to plant breeding. Unfortunately, current statistical methods and computer programs of QTL mapping are all designed for simple line crosses or multiple line crosses but under a regular mating system. It is not straightforward to extend the existing methods to handle multiple line crosses under irregular and complicated mating designs. The major hurdle comes from irregular inbreeding, multiple generations, and multiple alleles. In this study, we develop a Bayesian method implemented via the Markov chain Monte Carlo (MCMC) algorithm for mapping QTL using complicated multiple line crosses. With the MCMC algorithm, we are able to draw a complete path of the gene flow from founder alleles to their descendents via a recursive process. This has greatly simplified the problem caused by irregular mating and inbreeding in the mapping population. Adopting the reversible jump MCMC algorithm, we are able to simultaneously search for multiple QTL along the genome. We can even infer the posterior distribution of the number of QTL, one of the most important parameters in QTL study. Application of the new MCMC based QTL mapping procedure is demonstrated using two different mating designs. Design I involves two inbred lines and their derived F1, F2, and BC populations. Design II is a half-diallel cross involving three inbred lines. The two designs appear different, but can be handled with the same robust computer program.

Algorithms↗

Effects of zinc deficiency on rice growth and genetic factors contributing to tolerance.

Zinc (Zn) deficiency is the most widespread micronutrient disorder in rice (Oryza sativa), but efforts to develop cultivars with improved tolerance have been hampered by insufficient understanding of genetic factors contributing to tolerance. The objective of this paper was to examine alternative evaluation methods and to identify the most informative traits that would provide realistic information for rice breeders and to map quantitative trait loci (QTLs) associated with tolerance. Screening experiments in low-Zn nutrient solution and in a Zn-deficient field did not produce similar tolerance rankings in a set of segregating lines, which suggested that rhizosphere effects were of greater importance for lowland rice than internal Zn efficiency. The most severe symptom in the field was high plant mortality. The occurrence of leaf bronzing, usually regarded as indicative of susceptibility, did not necessarily concur with high plant mortality, which implied that both were under independent genetic control. The QTL mapping experiment conducted in the field with a population derived from a cross of IR74 (intolerant) with Jalmagna (tolerant) largely confirmed this. Four QTLs associated with plant mortality were detected, and only one of those colocalized with one of the four QTLs detected for leaf bronzing. The two most influential QTLs for plant mortality were detected on chromosomes 2 and 12. They explained 16.6% and 24.2% of the variation, and alleles of the tolerant donor parent Jalmagna reduced mortality by 16.6% and 14.8%, respectively. QTLs for plant mortality acted in a purely additive manner, whereas digenic epistatic interactions were important for leaf bronzing.

Gene Expression Regulation, Plant↗

Mixed-model QTL mapping for kernel hardness and dough strength in bread wheat.

Plant breeding data comprise unbalanced phenotypic data for inbreds with complex pedigrees. As traditional methods to map quantitative trait loci (QTL) cannot exploit plant breeding data, an alternative approach is QTL mapping via a mixed-model procedure. Our objective was to validate mixed-model QTL mapping for self-pollinated crops by detecting QTL for kernel hardness and dough strength from data in a bread wheat (Triticum aestivum L.) breeding program. We studied 80 parental and 373 experimental inbreds genotyped for 65 simple sequence repeat (SSR) markers and three candidate loci. The methodology involved three steps: variance component estimation, single-marker analyses, and a final multiple-marker analysis with marker effects treated as fixed effects. Two QTLs for kernel hardness were detected on chromosomes 1A (close to candidate locus GluA3) and 5D (close to candidate locus Ha). Four QTLs were detected for dough strength on chromosomes 1A, 1B, 1D, and 5B. Candidate gene GluA1, which was associated with dough strength, was the only candidate locus found significant. Results were consistent with previously reported markers and QTLs associated with kernel hardness and dough strength. Unlike previous studies that have assumed QTL effects as random, the assumption of fixed marker effects identified the favorable marker alleles to select for. We conclude that the detection of previously mapped QTL validates the usefulness of mixed-model QTL mapping in the context of a plant-breeding program.

Alleles↗

Interval mapping for loci affecting unordered categorical traits.

Many traits including shapes and colors of flowers, fruits and seeds in plants, as well as coat colors and some behavioral properties in animals, are recorded in discrete categories. If categories are ordered, genetic analyses of the categorical traits are often performed using the threshold model, which considers a latent continuous variable, called the liability, underlying a trait and assumes the monotonic relationship between the phenotype and the liability. In some categorical traits, however, descriptions of phenotypes are purely nominal and the phenotypic scores cannot be ordered. The threshold model is unreasonable for the analyses of such unordered categorical traits. In this study, we developed a method for interval mapping of loci affecting unordered categorical traits with more than two categories. The probability of the phenotype of an individual falling in each of the categories was expressed by a polychotomous logistic model, in which the log-odds for each category relative to the reference category were assumed to follow a linear model including genotype at a locus affecting a trait as covariate. Based on the model, the interval mapping using a maximum likelihood method was devised for the analysis of complex categorical traits described with unordered categories. We confined ourselves to the case of F2 populations derived from a cross between two inbred lines, although this approach can easily be extended to the analyses for other populations of general structures. As results of analyses of simulated data show, the method showed high efficiency in detecting the loci affecting unordered categorical traits.

Animals↗

Ovine alpha-amylase genes: isolation, linkage mapping and association analysis with milk traits.

On the basis of comparisons between cattle and sheep genome mapping information the ovine alpha-amylase gene was examined as a possible genetic marker for milk traits in sheep. The objective of the present study was to isolate, map and determine whether this gene is a candidate gene for milk traits. DNA fragments (832 and 2360 bp) corresponding to two different AMY genes were isolated, and one SNP in intron 3 and one GTG deletion in exon 3 of the 2360 bp DNA fragment were found. The 2360 bp ovine AMY DNA fragment was located on chromosome 1 by linkage mapping using the International Mapping Flock. No association was found between estimated breeding values for milk yield, protein and fat contents and AMY genotypes in a daughter design comprising 13 Manchega families with an average of 29 daughters (12-62) per sire.

Animals↗

A simple linear regression method for quantitative trait loci linkage analysis with censored observations.

Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however, they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using simulation we compare this method to both the Cox and Weibull proportional hazards models and a standard linear regression method that ignores censoring. The grouped linear regression method is of equivalent power to both the Cox and Weibull proportional hazards methods and is significantly better than the standard linear regression method when censored observations are present. The method is also robust to the proportion of censored individuals and the underlying distribution of the trait. On the basis of linear regression methodology, the grouped linear regression model is computationally simple and fast and can be implemented readily in freely available statistical software.

Chromosome Mapping↗

Quantitative trait loci modifying cardiac atrial septal morphology and risk of patent foramen ovale in the mouse.

Atrial septal defect (ASD) is a common congenital heart disease (CHD) occurring in 5 to 7 per 10,000 live births. Mutations in 5 human genes (NKX2.5, TBX5, GATA4, MYHC, ACTC) are known to cause dominant ASD, but these account for a minority of cases. Human and mouse data suggest that ASD exists in an anatomical continuum with milder septal variants patent foramen ovale (PFO) and atrial septal aneurysm, strongly associated with ischemic stroke and migraine. We have previously shown in inbred mice that the incidence of PFO strongly correlates with length of the interatrial septum primum, defining a quantitative trait underlying PFO risk. To better understand genetic causation of atrial septal abnormalities, we mapped quantitative trait loci (QTL) influencing septal morphology using mouse strains (QSi5 and 129T2/SvEms) maximally informative for PFO incidence and 3 quantitative septal anatomical traits including septum primum length. [QSi5x129T2/SvEms]F2 intercross animals (n=1437) were phenotyped and a whole genome scan performed at an average 17-cM interval. Statistical methodology scoring PFO as a binary phenotype was developed as a confirmatory mapping technique. We mapped 7 significant and 6 suggestive QTL modifying quantitative phenotypes, with 4 supported by binary analysis. Quantitative traits, although strongly associated with PFO (P<0.001), correlated poorly with each other and in all but 1 case QTL for different traits were nonoverlapping. Thus, multiple anatomical processes under separate genetic control contribute to risk of PFO. Our findings demonstrate the feasibility of modeling the genetic basis of common CHD using animal genetic and genomic technologies.

Animals↗

Accelerated congenics for mapping two blood pressure quantitative trait loci on chromosome 10 of Dahl rats.

OBJECTIVE: To localize quantitative trait loci (QTL) in an animal model that is potentially relevant to human hypertension. DESIGN AND METHODS: Four congenic strains have been constructed by replacing various segments of the Dahl salt-sensitive (S) rat by those of the Lewis (LEW) rat. A marker-assisted approach was employed to facilitate this process. When these congenic strains were established, their blood pressures (BPs) were measured by telemetry and compared with that of the S rat. Moreover, a search was conducted to find possible intermediate phenotypes linking the BP effects of the QTL and other physiological traits. RESULTS: Two BP QTL, designated as QTL1 and QTL2, have been mapped to the regions of 4.2 centiMorgans (cM) and less than 12.1 cM respectively on rat chromosome 10. The effects of both QTL correlate with cardiac, left ventricular and aortic hypertrophy. The effect of QTL1 is also associated with renal hypertrophy. CONCLUSION: The current study proved that multiple QTL exist in the region of Dahl rat chromosome 10. The identification of these QTL may help unravel the mechanisms underlying the pathogenesis of certain QTL in humans.

Animals↗

Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster.

Previously, we mapped quantitative trait loci (QTL) affecting response to short-term selection for abdominal bristle number to seven suggestive regions that contain loci involved in bristle development and/or that have adult bristle number mutant phenotypes, and are thus candidates for bristle number QTL in natural populations. To test the hypothesis that the factors contributing to selection response genetically interact with these candidate loci, high and low chromosomes from selection lines were crossed to chromosomes containing wild-type or mutant alleles at the candidate loci, and the numbers of bristles were recorded in trans heterozygotes. Quantitative failure to complement, detected as a significant selection line*cross effect by analysis of variance, can be interpreted as evidence for allelism or epistasis between the factors on selected chromosomes and the candidate loci. Mutations at some candidate loci (bb, emc, h, Dl, Hairless) showed strong interactions with selected chromosomes, whereas others interacted weakly (ASC, abd, Scr) or not at all (N, mab, E(spl)). These results support the hypothesis that some candidate loci, initially identified through mutations of large effect on bristle number, either harbor or are close members in the same genetic pathway as variants that contribute to standing variation in bristle number.

Alleles↗

DGAT1, a new positional and functional candidate gene for intramuscular fat deposition in cattle.

Intramuscular fat content, also assessed as marbling of meat, represents an important beef quality trait. Recent work has mapped a quantitative trait locus (QTL) with an effect on marbling to the centromeric region of bovine chromosome 14, with the gene encoding thyroglobulin (TG) being proposed as a positional and functional candidate gene for this QTL. Recently, the gene encoding diacylglycerol O-acyltransferase (DGAT1), which also has been mapped within the region of the marbling QTL, has been demonstrated to affect the fat content of milk. In the present study, the effects of a 5'-polymorphism of TG and of a lysine/alanine polymorphism of DGAT1 on the fat content of musculus (m.) semitendinosus and m. longissimus dorsi in 55 bovine animals (28 German Holstein and 27 Charolais) has been investigated. Significant effects were found for both candidate genes in both the breeds. These effects seem to be independent of one another because the alleles of the two polymorphisms showed no statistically significant disequilibrium. The DGAT1 effect is mainly on the m. semitendinosus. The TG polymorphism only affects m. longissimus dorsi. However, both intramuscular fat enhancing effects seem to be recessive. The possibility of two linked loci, acting recessively on intramuscular fat content, will require special strategies when selecting for higher marbling scores.

Acyltransferases↗

QTLs mapping for fruit size and shape in chromosomes 2 and 4 in pepper and a comparison of the pepper QTL map with that of tomato.

Quantitative trait locus (QTL) mapping for fruit weight and shape in pepper (Capsicum spp.) was performed using C. chinense and C. frutescens introgression lines of chromosomes 2 and 4. In chromosome 2, a single major fruit-weight QTL, fw2.1, was detected in both populations that explained 62% of the trait variation. This QTL, as well as a fruit-shape QTL, fs2.1, which had a more minor effect, were localized to the tomato fruit-shape gene ovate. The cloned tomato fruit-weight QTL, fw2.2, did not play a major role in controlling fruit size variations in pepper. In chromosome 4, two fruit-weight QTLs, fw4.1 and fw4.2, were detected in the same genomic regions in both mapping populations. In addition, a single fruit-shape QTL was detected in each of the mapping populations that co-localized with one of the fruit-weight QTLs, suggesting pleiotropy or close linkage of the genes controlling size and shape. fw2.1 and fw4.2 represent major fruit-weight QTLs that are conserved in the three Capsicum species analyzed to date for fruit-size variations. Co-localization of the pepper QTLs with QTLs identified for similar traits in tomato suggests that the pepper and tomato QTLs are orthologous. Compared to fruit-shape QTLs, fruit-weight QTLs were more often conserved between pepper and tomato. This implies that different modes of selection were employed for these traits during domestication of the two Solanaceae species.

Capsicum↗

High-resolution genetic mapping of the ACE-linked QTL influencing circulating ACE activity.

Fine-mapping of trait loci through combined linkage and association analysis is an important component of strategies designed to identify causative gene variants, particularly in situations where the trait may be influenced by one or more of many polymorphisms within the same gene. Angiotensin-1 converting enzyme (ACE) provides one of the best models for developing and testing such methodologies, as a major fraction of the heritable variation in the activity of the angiotensin-1 converting enzyme (ACE) is tightly linked to the ACE gene. Moreover, ACE contains many frequent polymorphisms that are in strong linkage disequilibrium with each other. Although none of these variants induces a significant amino-acid change, one or more, either singly or in combination, are likely to have a strong effect on the quantitative phenotype. Here, we show that measured-haplotype analysis of SNP data from a large European family cohort can be used to localise the major ACE-linked genetic factors influencing the trait to a 16 kb interval within the gene, thus limiting the number of ACE variants that need to be considered in future studies designed to elucidate their biological effects. The approaches developed will be applicable to the fine-mapping of other quantitative trait loci in humans.

Amino Acid Substitution↗

Detection of QTLs for Stagonospora glume blotch resistance in Swiss winter wheat.

Stagonospora nodorum is the causal agent of the Stagonospora glume blotch disease in hexaploid wheat. The Swiss winter bread wheat cv. 'Arina' has a highly effective, durable and quantitative glume blotch resistance. We studied 240 single seed descent (SSD)-derived lines of an 'Arina x Forno' F(5:7) population to identify and map quantitative trait loci (QTLs) for glume blotch resistance under natural infestation. Using composite interval mapping (CIM) and LOD>4.5, we detected two chromosomal regions on chromosome arms 3BS and 4BL which were specifically associated with glume blotch resistance. These identified QTLs were designated QSng.sfr-3BS and QSng.sfr-4BL, respectively. QSng.sfr-3BS peaked at the locus Xgwm389 in the telomeric region of the short arm of chromosome 3B and explained 31.2% of the observed phenotypic variance for the resistance within the population. The responsible QSng.sfr-3BS allele originated from the resistant parent 'Arina'. The QTL QSng.sfr-4BL (19.1%) mapped to chromosome arm 4BL ('Forno' allele) very close to two known genes, TaMlo and a catalase ( Cat). Both QTL alleles combined could enhance the resistance level by about 50%. Additionally, they showed significant epistatic effects (4.4%). We found PCR-based microsatellite markers closely linked to QSng.sfr-3BS (gwm389) and QSng.sfr-4BL (gwm251) which make marker-assisted selection (MAS) for Stagonospora glume blotch resistance feasible. We also found one resistance QTL, QSng.sfr-5BL, on the long arm of chromosome 5B which overlapped with QTLs for plant height as well as heading time.

Alleles↗