The evolution of genetic architectures underlying quantitative traits

In the classic view introduced by R. A. Fisher, a quantitative trait is encoded by many loci with small, additive effects. Recent advances in quantitative trait loci mapping have begun to elucidate the genetic architectures underlying vast numbers of phenotypes across diverse taxa, producing observations that sometimes contrast with Fisher''s blueprint. Despite these considerable empirical efforts to map the genetic determinants of traits, it remains poorly understood how the genetic architecture of a trait should evolve, or how it depends on the selection pressures on the trait. Here, we develop a simple, population-genetic model for the evolution of genetic architectures. Our model predicts that traits under moderate selection should be encoded by many loci with highly variable effects, whereas traits under either weak or strong selection should be encoded by relatively few loci. We compare these theoretical predictions with qualitative trends in the genetics of human traits, and with systematic data on the genetics of gene expression levels in yeast. Our analysis provides an evolutionary explanation for broad empirical patterns in the genetic basis for traits, and it introduces a single framework that unifies the diversity of observed genetic architectures, ranging from Mendelian to Fisherian.     

The FIC1 gene: structure and polymorphisms in baboon

A genome scan performed on 648 pedigreed baboons to detect and localize quantitative trait loci (QTL) for lipoprotein phenotypes that are known risk factors for atherosclerosis indicated the presence of a QTL on chromosome 18q that exerts a major influence on HDL-cholesterol (HDL-C) related phenotypes. Inspection of the human gene map revealed that the familial intrahepatic cholestatis gene 1 (FIC1) maps to the homologous region of baboon chromosome 18 containing the major QTL influencing HDL-C phenotypes. FIC1 is a strong biological candidate for this QTL because HDL-C is the preferred precursor for bile acid synthesis. In this study, we cloned and sequenced FIC1 cDNA and found that it is highly conserved between human and baboon. We also sequenced FIC1 cDNAs from a panel of unrelated baboons revealing single nucleotide polymorphisms (SNPs) and a polymorphic dinucleotide repeat. None of the baboon SNPs corresponded to human FIC1 mutations associated with familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis disorders.     

质量性状和数量性状含义的辨析

植物或动物的性状一般分为质量性状和数量性状,而实际上,许多性状并不是绝对的质量性状或数量性状,而是同时受到一个或少数几个主基因和或数量性状多基因的控制.因此,在遗传学教学中,有必要对此类性状进行分析.为加深学生对此类性状的遗传及这两个概念的理解,通过性状次数分布图分析,结合最新的遗传学研究成果,对之进行了分析和讨论.     

Evidence of linkage between high-glycine-tyrosine keratin gene loci and wool fibre diameter in a Merino half-sib family

Candidate genes for quantitative trait loci have been studied in a Medium Peppin Merino flock. Obvious candidates for effects on wool production traits are genes for the major proteins expressed in the wool fibre, the keratin and keratin-associated protein genes. Two keratin-associated protein loci, KRTAP6 and KRTAP8, have previously been shown to be linked. The results of analyses between these two loci and production traits gave significant evidence of linkage with wool fibre diameter in one out of eight halfsib groups tested. High-glycine-tyrosine proteins (KRTAP6, 7 and 8) are known to vary considerably in abundance in wool fibres and it is possible that a gene for major effect on fibre diameter is located within the same chromosomal region as KRTAP6 and KRTAP8.     

Quantitative trait loci for red blood cell traits in swine

Haematological traits are essential diagnostic parameters in veterinary practice but knowledge on the genetic architecture controlling variability of erythroid traits is sparse, especially in swine. To identify QTL for erythroid traits in the pig, haematocrit (HCT), haemoglobin (HB), erythrocyte counts (RBC) and mean corpuscular haemoglobin content (MCHC) were measured in 139 F₂ pigs from a Meishan/Pietrain family, before and after challenge with the protozoan pathogen Sarcocystis miescheriana . The pigs passed through three stages representing acute disease, reconvalescence and chronic disease. Forty-three single QTL controlling erythroid traits were identified on 16 chromosomes. Twelve of the QTL were significant at the genome-wide level while 31 were significant at a chromosome-wide level. Because erythroid traits varied with health and disease status, QTL influencing the erythroid phenotypes showed specific health/disease patterns. Regions on SSC5, 7, 8, 12 and 13 contained QTL for baseline erythroid traits, while the other QTL regions affected distinct stages of the disease model. Single QTL explained 9–17% of the phenotypic variance in the F₂ animals. Related traits were partly under common genetic influence. Our analysis confirms that erythroid trait variation differs between Meishan and Pietrain breeds and that this variation is associated with multiple chromosomal regions.     

Quantitative trait loci segregating in crosses between New Hampshire and White Leghorn chicken lines: I. egg production traits

A genome scan was performed to detect chromosomal regions that affect egg production traits in reciprocal crosses between two genetically and phenotypically extreme chicken lines: the partially inbred line New Hampshire (NHI) and the inbred line White Leghorn (WL77). The NHI line had been selected for high growth and WL77 for low egg weight before inbreeding. The result showed a highly significant region on chromosome 4 with multiple QTL for egg production traits between 19.2 and 82.1 Mb. This QTL region explained 4.3 and 16.1% of the phenotypic variance for number of eggs and egg weight in the F₂ population, respectively. The egg weight QTL effects are dependent on the direction of the cross. In addition, genome‐wide suggestive QTL for egg weight were found on chromosomes 1, 5, and 9, and for number of eggs on chromosomes 5 and 7. A genome‐wide significant QTL affecting age at first egg was mapped on chromosome 1. The difference between the parental lines and the highly significant QTL effects on chromosome 4 will further support fine mapping and candidate gene identification for egg production traits in chicken.     

Expression quantitative trait loci: present and future

The last few years have seen the development of large efforts for the analysis of genome function, especially in the context of genome variation. One of the most prominent directions has been the extensive set of studies on expression quantitative trait loci (eQTLs), namely, the discovery of genetic variants that explain variation in gene expression levels. Such studies have offered promise not just for the characterization of functional sequence variation but also for the understanding of basic processes of gene regulation and interpretation of genome-wide association studies. In this review, we discuss some of the key directions of eQTL research and its implications.     

家禽数量性状基因座定位的研究进展

近二十年来,各种DNA标记技术及相关生物技术的发展和完善为高密度、覆盖面广的连锁图谱的构建及QTL的定位奠定了基础,本就目前世界上建立的几个较有影响的资源家系、各种DNA标记技术、家禽中定位的QTL及存在问题等方面作一综述。     

Use of recombinant inbred strains to map genes of aging

Recombinant inbred strains have been used in a number of organisms for segregation and linkage analysis of quantitative traits. One major advantage of the recombinant inbred (RI) methodology is that the genetic identity of individuals within a strain permits replicate measures of the same recombinant genotype. Such replicability is important for traits such as aging inDrosophila, where phenotypic expression is highly influenced by different environmental conditions. RI strain methodology has an added advantage for DNA marker-based linkage analysis of traits measured over the lifespan of the organism. The DNA can be extracted from individuals of the same genotype as those measured in a longevity study. In this paper an argument is presented for the use of a set of recombinant inbred strains to map the quantitative trait loci involved in the aging process inDrosophila. A unique use of a set of stable, transposable moleular markers to trace the quantitative trait loci involved is suggested.     

Genetic markers linked to quantitative traits in poultry

This study utilized DNA fingerprints and crosses of two genetically distinct lines of layer-type chickens to identify genetic markers linked to quantitative trait loci (QTL). In phase I, back-cross (BC¹) hens were separately ranked for each of eight traits and then blood pools were produced in groups along each phenotypic distribution. The DNA was isolated from the blood pools and used in a gradient analysis to screen for DNA fingerprint bands that exhibited intensity gradients associated with the phenotypic traits. To identify linkage of bands with QTL and to estimate band effects, F₂ progeny were produced in phase II from the phase I BC, population. A single-trait animal model was used for analysis of associations of all individual DNA fingerprint bands of sires and their progeny phenotypic performance. Twenty fingerprint bands, only two of which had shown trait-associated gradients in phase I, were identified by the animal model analysis of the progeny test as QTL linked (P≤005) to specific traits of growth, reproduction and egg quality. These 20 bands warrant further study as potentially valuable molecular markers for QTL.     

Quantitative trait loci with additive effects on palatability and fatty acid composition of meat in a Wagyu-Limousin F2 population

A whole-genome scan was conducted on 328 F(2) progeny in a Wagyu x Limousin cross to identify quantitative trait loci (QTL) affecting palatability and fatty acid composition of beef at an age-constant endpoint. We have identified seven QTL on five chromosomes involved in lipid metabolism and tenderness. None of the genes encoding major enzymes involved in fatty acid metabolism, such as fatty acid synthase (FASN), acetyl-CoA carboxylase alpha (ACACA), solute carrier family 2 (facilitated glucose transporter) member 4 (SLC2A4), stearoyl-CoA desaturase (SCD) and genes encoding the subunits of fatty acid elongase, was located in these QTL regions. The present study may lead to a better-tasting and healthier product for consumers through improved selection for palatability and lipid content of beef.     

A genome scan with AFLP markers to detect fearfulness-related QTLs in Japanese quail

A quantitative trait loci (QTL) study was undertaken to identify genome regions involved in the control of fearfulness in Japanese quail (Coturnix japonica). An F2 cross was made between two quail lines divergently selected over 29 generations on duration of tonic immobility (DTI), a catatonic-like state of reduced responsiveness to a stressful stimulation. A total of 1065 animals were measured for the logarithm of DTI (LOGTI), the number of inductions (NI) necessary to induce the immobility reaction, open-field behaviour including locomotor activity (MOVE), latency before first movement (LAT), number of jumps (JUMP), dejections (DEJ) and shouts (SHOUT), corticosterone level after a contention stress (LOGCORT) and body weight at 2 weeks of age (BW2). A total of 310 animals were included in a genome scan using selective genotyping with 248 AFLP markers. A total of 21 suggestive or genome-wide significant QTL were observed. Two highly significant QTL were identified on linkage group 1 (GL1), one for LOGTI and one for NI. In the vicinity of the QTL for LOGTI, a nearly significant QTL for SHOUT and a suggestive QTL for LAT were also identified. On GL3, genome-wide significant QTL were observed for JUMP and DEJ as well as suggestive QTL for LOGTI, MOVE, SHOUT and LAT. A significant QTL for BW2 was observed on GL2 and a nearly significant one on GL1. These results may be useful in the understanding of fearfulness in quail and related species provided that fearfulness has the same genetic basis.     

Identification of a 3.7-Mb region for a marbling QTL on bovine chromosome 4 by identical-by-descent and association analysis

QTL mapping for growth and carcass traits was performed using a paternal half-sib family composed of 325 Japanese Black cattle offspring. Nine QTL were detected at the 1% chromosome-wise significance level at a false discovery rate of less than 0.1. These included two QTL for marbling on BTA 4 and 18, two QTL for carcass weight on BTA 14 and 24, two QTL for longissimus muscle area on BTA 1 and 4, two QTL for subcutaneous fat thickness on BTA 1 and 15 and one QTL for rib thickness on BTA 6. Although the marbling QTL on BTA 4 has been replicated with significant linkages in two Japanese Black cattle sires, the three Q (more marbling) haplotypes, each inherited maternally, were apparently different. To compare the three Q haplotypes in more detail, high-density microsatellite markers for the overlapping regions were developed within the 95% CIs (65 markers in 44–78 cM). A detailed haplotype comparison indicated that a small region (<3.7 Mb) around 46 cM was shared between the Qs of the two sires, whose dams were related. An association of this region with marbling was shown by a regression analysis using the local population, in which the two sires were produced and this was confirmed by an association study using a population collected throughout Japan. These results strongly suggest that the marbling QTL on BTA 4 is located in the 3.7-Mb region at around 46 cM.