Quantitative Trait Loci Analysis in Animals

by J. I. Weller

• ISBN13: 9780851994024
• ISBN10: 0851994024
• Format: Paperback
• Copyright: 2001-11-08
• Publisher: Oxford University Press, USA

Summary

Detection of Quantitative Trait Loci (QTL) has become a 'hot' topic in genetics in recent years and is of major agricultural significance. This advanced textbook describes the scientific literature and principles on methods for quantitative trait loci detection and analysis and marker assisted selection in animal breeding.No other similar textbook in this areaAuthor has excellent reputation in the fieldThis is a new and dynamically developing area of research, of worldwide interest

Table of Contents

Preface, theory vs. results	1	(3)
Historical overview	3	(12)
Introduction	3	(1)
From Mendel to Sax	3	(2)
Quantitative genetics 1920-1980, or who needs Mendel?	5	(1)
QTL detection 1930-1980, theory and experiments	6	(1)
From biochemistry to biotechnology, or more markers than we will ever need	7	(2)
Genetic mapping functions	9	(3)
Physical and genetic mapping, questions of scale	12	(2)
Summary	14	(1)
Principles of Parameter Estimation	15	(15)
Introduction	15	(1)
Desired properties of QTL parameter estimates	16	(1)
Moments method of estimation	17	(1)
Least-squares parameter estimation	17	(1)
Least-squares solutions for a single parameter	18	(1)
Least-squares solutions for the general linear model	19	(1)
Maximum likelihood estimation for a single parameter	20	(2)
Maximum likelihood multi-parameter estimation	22	(1)
Confidence intervals and hypothesis testing for MLE	23	(1)
Methods to maximize likelihood functions	24	(1)
Derivative-free methods	25	(1)
Second derivative-based methods	26	(1)
First derivative-based methods (EM)	26	(1)
Bayesian estimation	27	(1)
Minimum difference estimation	28	(1)
Summary	29	(1)
Random and Fixed Effects, the Mixed Model	30	(18)
Introduction	30	(1)
The mixed linear model	30	(2)
The mixed model equations	32	(1)
Solving the mixed model equations	33	(1)
Some important properties of mixed model solutions	34	(1)
Equation absorption	34	(1)
Multivariate mixed model analysis	35	(2)
The repeatability model	37	(1)
The individual animal model	38	(1)
Grouping individuals with unknown ancestors	39	(1)
The reduced animal model	40	(1)
Maximum likelihood estimation with mixed models	41	(1)
Estimation of variance components, analysis of variance type methods	41	(1)
Maximum likelihood estimation of variance components	42	(3)
Restricted maximum likelihood estimation of variance components	45	(1)
The problem of variance components outside the parameter space	46	(1)
Summary	47	(1)
Experimental Designs to Detect QTL, Generation of Linkage Disequilibrium	48	(27)
Introduction	48	(1)
Assumptions, problems and types of effects postulated	48	(4)
Experimental designs for detection of QTL in crosses between inbred lines	52	(1)
Linear model analysis of crosses between inbred lines	53	(4)
Experimental designs for detection of QTL in segregating populations - general considerations	57	(3)
Experimental designs for detection of QTL in segregating populations - large families	60	(3)
Experimental designs for detection of QTL in segregating populations - small families	63	(4)
Experimental designs based on additional generations	67	(3)
Comparison of the expected contrasts for different experimental designs	70	(1)
Gametic effect models for complete population analyses	71	(2)
Summary	73	(2)
QTL Parameter Estimation for Crosses between Inbred Lines	75	(21)
Introduction	75	(1)
Moments method of estimation	76	(1)
Least-squares estimation of QTL parameters	77	(4)
Least-squares estimation of QTL location for sib-pair analysis with flanking markers	81	(2)
Linear regression mapping of QTL with flanking markers	83	(2)
Marker information content for interval mapping, uninformative and missing marker genotypes	85	(2)
Maximum likelihood QTL parameter estimation for crosses between inbred lines and a single marker	87	(1)
Maximum likelihood tests of significance for a segregating	88	(1)
Maximum likelihood QTL parameter estimation for crosses between inbred lines and two flanking markers	89	(1)
Estimation of QTL parameters by the expectation-maximization algorithm	90	(2)
Biases in estimation of QTL parameters with interval mapping	92	(1)
The likelihood ratio test with interval mapping	93	(1)
Summary	94	(2)
Advanced statistical methods for QTL detection and parameter estimation	96	(24)
Introduction	96	(1)
Higher order QTL effects	97	(1)
QTL interaction effects	97	(2)
Simultaneous analysis of multiple marker brackets	99	(2)
Principles of composite interval mapping	101	(1)
Properties of composite interval mapping	101	(1)
Derivation of maximum likelihood parameter estimates by composite interval mapping	102	(1)
Hypothesis testing with composite interval mapping	103	(1)
Multi-marker and QTL analysis by regression of phenotype on marker genotypes	104	(1)
Estimation of QTL parameters in outbred propulations	105	(2)
Solutions for analysis of field data from segregating populations	107	(2)
Maximum likelihood analysis of QTL parameters for the daughter design with linkage to a single marker	109	(2)
Maximum likelihood estimation of QTL parameters from other complex pedigrees	111	(1)
Non-linear regression estimation for complex pedigrees	112	(2)
Maximum likelihood estimation with random effects included in the model	114	(1)
Maximum likelihood estimation of QTL effects on categorical traits	115	(2)
Estimation of QTL effects with the threshold model	117	(1)
Estimation of QTL effects on disease traits by the allele-sharing method	118	(1)
Summary	119	(1)
Analysis of QTL as Random Effects	120	(22)
Introduction	120	(1)
ML estimation of variance components for the Haseman-Elston sib-pair model	121	(2)
The random gametic model of Fernando and Grossman, computing Gv	123	(2)
Computing the inverse of Gv	125	(1)
Analysis of the random gametic model by a reduced animal model (RAM)	126	(2)
Analysis of the random gametic QTL model with multiple QTL and marker brackets	128	(1)
Computation of the gametic effects variance matrix	129	(2)
The gametic effect model for crosses between inbred lines	131	(1)
REML estimation of the QTL variance and recombination for the model of Fernando and Grossman	132	(1)
REML estimation of the QTL variance and location with marker brackets	133	(1)
Bayesian estimation of QTL effects, determining the prior distribution	134	(4)
Formula for Bayesian estimation and tests of significance of a segregating QTL in a simulated grand-daughter design	138	(1)
Comparison of ML and Bayesian analyses of a simulated grand-daughter design	139	(1)
Markov Chain Monte Carlo algorithms, Gibbs' sampling	140	(1)
Summary	141	(1)
Statistical Power to Detect QTL, and Parameter Confidence Intervals	142	(15)
Introduction	142	(1)
Estimation of power in crosses between inbred lines	143	(1)
Replicate progeny in crosses between inbred lines	144	(2)
Estimation of power for segregating populations	146	(4)
Power estimates for likelihood ratio tests - general considerations	150	(1)
The effect of statistical methodology on the power of QTL detection	150	(1)
Estimation of power with random QTL models	151	(1)
Confidence intervals for QTL parameters - analytical methods	152	(1)
Simulation studies of confidence intervals	153	(1)
Empirical methods to estimate CI, parametric and non-parametric bootstrap and jackknife methods	154	(2)
Summary	156	(1)
Optimization of Experimental Designs	157	(12)
Introduction	157	(1)
Economic optimization of marker spacing when the number of individuals genotyped is non-limiting	157	(1)
Economic optimization with replicate progeny	158	(2)
Selective genotyping	160	(3)
Sample pooling - general considerations	163	(1)
Estimation of power with sample pooling	163	(3)
Comparison of power and sample sizes with random genotyping, selective genotyping, and sample pooling	166	(1)
Sequential sampling	167	(1)
Summary	168	(1)
Fine Mapping of QTL	169	(9)
Introduction	169	(1)
Determination of the genetic map critical interval for a marker locus with a saturated genetic marker map	169	(2)
Confidence interval for QTL location with a saturated genetic marker map	171	(1)
Fine mapping of QTL via advanced intercross lines	172	(1)
Selective phenotyping	173	(1)
Recombinant progeny testing	174	(1)
Interval specific congenic strains	174	(2)
Recombinant inbred segregation test	176	(1)
Fine mapping of QTL in outcrossing populations by identity by descent	176	(1)
Summary	177	(1)
Complete Genome QTL Scans - the Problem of Multiple Comparisons	178	(12)
Introduction	178	(1)
Multiple markers and whole genome scans	179	(2)
QTL detection by permutation tests	181	(1)
QTL detection based on the false discovery rate	181	(4)
A priori determination of the proportion of false positives	185	(1)
Analysis of multiple pedigrees	186	(2)
Biases with estimation of multiple QTL	188	(1)
Summary	189	(1)
Multiple Trait QTL analysis	190	(15)
Introduction	190	(1)
Problems and solutions for multiple trait QTL analyses	190	(1)
Multivariate estimation of QTL parameters for correlated traits	191	(2)
Comparison of power for single and multitrait QTL analyses	193	(3)
Pleiotropy vs. linkage	196	(1)
Estimation of QTL parameters for correlated traits by canonical transformation	197	(2)
Determination of statistical significance for multitrait analyses	199	(1)
Selective genotyping with multiple traits	200	(3)
Summary	203	(2)
Principles of Selection Index and Traditional Breeding Programmes	205	(12)
Introduction	205	(1)
Selection index for a single trait	205	(2)
Changes in QTL allelic frequencies due to selection	207	(1)
Multitrait selection index	208	(1)
The value of genetic gain	209	(2)
Dairy cattle breeding programmes, half sib and progeny tests	211	(3)
Nucleus breeding schemes	214	(1)
Summary	215	(2)
Marker-assisted Selection - Theory	217	(10)
Introduction	217	(1)
Situations in which selection index is inefficient	217	(1)
Potential contribution of MAS for selection within a breed - general considerations	218	(1)
Phenotypic selection vs. MAS for individual selection	219	(1)
MAS for sex-limited traits	220	(1)
Two-stage selection: MAS on juveniles and phenotypic selection of adults	221	(1)
MAS including marker and phenotypic information on relatives	222	(1)
Maximum selection efficiency of MAS with all QTL known, relative to trait-based selection, and the reduction in RSE due to sampling variance	223	(1)
Marker information in segregating populations	224	(1)
Inclusion of marker information in ``animal model'' genetic evaluations	225	(1)
Velogenetics - the synergistic use of MAS and germ-line manipulation	225	(1)
Summary	226	(1)
Marker-assisted Selection - Results of Simulation Studies	227	(16)
Introduction	227	(1)
Modeling the polygenic variance	227	(2)
The effective number of QTL	229	(1)
Proposed dairy cattle breeding schemes with MAS - overview	230	(1)
Inclusion of marker information into standard progeny test and MOET nucleus breeding schemes	230	(2)
Progeny test schemes, in which information on genetic markers is used to preselect young sires	232	(2)
Selection of sires based on marker information without a progeny test	234	(1)
Long-term considerations, MAS vs. selection index	235	(3)
MAS for a multitrait breeding objective with a single identified QTL	238	(3)
MAS for a multitrait breeding objective with multiple identified QTL	241	(1)
Summary	241	(2)
Marker-assisted Introgression	243	(7)
Introduction	243	(2)
Marker-assisted introgression - general considerations	245	(1)
Marker-assisted introgression of a major gene into an inbred line	246	(1)
Marker-assisted introgression of a QTL into a donor population under selection	247	(1)
Marker-assisted introgression for multiple genes	248	(1)
Summary	249	(1)
Glossary of commonly used symbols	250	(11)
Latin symbols	250	(8)
Greek symbols	258	(2)
Other symbols	260	(1)
References	261	(13)
Author index	274	(3)
Subject index	277