Economic Trait Loci Research Articles

A high‐resolution comparative radiation hybrid map of ovine chromosomal regions that are homologous to human chromosome 6 (HSA6)

In this study, we constructed high-resolution radiation hybrid (RH) and comparative maps of ovine chromosomes or chromosomal segments that are homologous to human chromosome 6 (HSA6). A total of 251 markers were successfully genotyped across the recently developed USUoRH5000 whole-genome panel; 208 of these markers were assigned to five RH linkage groups distributed on three ovine chromosomes (OAR8, 9 and 20). The RH maps have good correspondence with previous chromosome painting data, although a small centromeric region on OAR9 that is homologous to HSA6 had not been previously detected using human chromosome paints on ovine chromosomal spreads. High percentages of the ovine markers were identified as orthologues in the bovine (86.3%), dog (85.8%), horse (69.3%) and human (88.7%) genomes. These maps contribute to investigations in mammalian chromosome evolution and the search for economic trait loci in sheep.

Utilización de información molecular en programas de mejoramiento animal

La genómica es la subdisciplina de la genética que tiene por objeto la caracterización molecular de genomas completos; así, desde hace algunos años se han llevado a cabo múltiples trabajos en casi todas las especies de animales domésticos con el fin de localizar regiones cromosómicas que pueden afectar los caracteres de mayor interés económico en la producción animal. En el presente artículo se revisan estrategias de genómica que, en combinación con las metodologías de genética cuantitativa, se están aplicando en programas de mejoramiento animal. Una de dichas estrategias es la detección de QTL (Quantitative Trait Loci) o ETL (Economic Trait Loci), términos que se refieren a regiones de ADN que ejercen un efecto significativo sobre una o varias características fenotípicas. Además, se muestra que la incorporación de la información que proporcionan los avances en genómica en los programas de mejoramiento tradicionales comienza a ser una realidad que se lleva a cabo mediante herramientas de genética cuantitativa, lo que se denomina de una forma genérica ‘selección asistida por marcadores’ (MAS, Marker Assisted Selection). Por último, se hace un análisis sobre el considerable incremento de la información molecular que puede ser utilizada en programas de mejoramiento de animales domésticos, y cómo los agentes tradicionalmente implicados en procesos de selección, como las asociaciones de criadores y los centros nacionales o regionales de evaluación genética, pueden tener acceso, total o restringido, a los resultados de los estudios de genética molecular. La genómica es la subdisciplina de la genética que tiene por objeto la caracterización molecular de genomas completos; así, desde hace algunos años se han llevado a cabo múltiples trabajos en casi todas las especies de animales domésticos con el fin de localizar regiones cromosómicas que pueden afectar los caracteres de mayor interés económico en la producción animal. En el presente artículo se revisan estrategias de genómica que, en combinación con las metodologías de genética cuantitativa, se están aplicando en programas de mejoramiento animal. Una de dichas estrategias es la detección de QTL (Quantitative Trait Loci) o ETL (Economic Trait Loci), términos que se refieren a regiones de ADN que ejercen un efecto significativo sobre una o varias características fenotípicas. Además, se muestra que la incorporación de la información que proporcionan los avances en genómica en los programas de mejoramiento tradicionales comienza a ser una realidad que se lleva a cabo mediante herramientas de genética cuantitativa, lo que se denomina de una forma genérica ‘selección asistida por marcadores’ (MAS, Marker Assisted Selection). Por último, se hace un análisis sobre el considerable incremento de la información molecular que puede ser utilizada en programas de mejoramiento de animales domésticos, y cómo los agentes tradicionalmente implicados en procesos de selección, como las asociaciones de criadores y los centros nacionales o regionales de evaluación genética, pueden tener acceso, total o restringido, a los resultados de los estudios de genética molecular.

Prospects for whole genome linkage disequilibrium mapping in thoroughbreds

Linkage disequilibrium (LD) mapping is often used in searches for genes governing economically significant traits and diseases. The D′ coefficient is a commonly used measure of the extent of LD between all possible pairs of alleles at two markers. This study aimed to test the utility of the D′ coefficient for LD mapping of a trait in a thoroughbred population. Microsatellite genotype data and grey coat colour as a trait model in a thoroughbred population were used to assess the extent of LD. We demonstrated that LD mapping was a reasonable approach for initial genome-wide scans in a thoroughbred population. Significant LD was demonstrated at approximately 7 cM, implying that roughly 430 appropriately spaced microsatellites were needed for systematic whole-genome LD mapping in this model. LD mapping methods using D′ in a thoroughbred population were useful for identifying the chromosomal regions for diseases and economic trait loci (ETL). It was suggested that a thoroughbred population represented a population particularly suitable for LD mapping.

Genomic approaches to economic trait loci and tissue expression profiling: application to muscle biochemistry and beef quality

Genetic and environmental factors profoundly alter the phenotypes of animals. Nowadays, genomics allows large-scale analysis of gene characteristics (structural genomics) and expression (functional genomics). Genome mapping, comparative genomics and identification of quantitative trait loci and polymorphisms are the subject of active investigation to gain a better knowledge of the structure and function of genes. Gene expression profiling using DNA microarrays and proteomics holds great promise for the study of regulatory events which control the final biological functions. Combined with classical genetics and muscle biochemistry to form an integrative biology, these new approaches will bring a better understanding of complex traits and physiological processes. Major applications in meat science could be, for cattle, (1) the identification of new predictors of quality traits (for instance, tenderness), (2) the monitoring of beef quality (including traceability) through the production systems (nutrition level, growth path, grass-feeding), and (3) the improvement of animal selection (markers and gene assisted selection) which may also include quality traits.

An extensive and comprehensive radiation hybrid map of bovine Chromosome 15: comparison with human Chromosome 11.

An extensive and comprehensive radiation hybrid map of bovine Chromosome 15 (BTA15) was built with 42 anonymous markers, 3 ESTs, and 49 genes. This work allows us to refine the comparative map between human Chromosome (Chr) 11 (HSA11) and BTA15. Four blocks with a similar gene content and relatively good gene order conservation were identified. The discrepancies are concentrated on closely positioned genes for which discrimination is not possible between mapping resolution limits in either the human or the bovine maps and true local inversions. Using the gene order similarity and the human physical map as starting point, we estimated the overall physical length of BTA15 to be around 75.3 Mb. The INRA bovine BAC library was screened for all the markers ordered on the bovine map, which will provide anchors for future efforts in the construction of a physical map of the bovine genome.Finally, this map contains the majority of publicly available polymorphic markers described for BTA15 and integrates those with comparative mapping information. It should, therefore, constitute a powerful tool in the identification of relevant candidate genes in regions of BTA15 harboring economic trait loci.

Genomic tools to improve parasite resistance

The natural genetic variability of the ruminant immune system provides a feasible means to control gastrointestinal (GI) parasite infection without anthelmintics. However, the paradigm of traditional selection has not been effectively applied to the moderately heritable traits of parasite resistance ( h≈0.3) due to the difficulty and expense of gathering accurate phenotypes in a commercial production setting. These characteristics make host traits related to GI nematode infection ideal candidates for genomics-based research. To initiate explanation of important allelic differences, economic trait loci (ETL) are being identified and mapped using a resource population of Angus cattle segregating for GI nematode resistance and susceptibility to the two most common nematode parasites of US cattle, Ostertagia ostertagi and Cooperia oncophora. The population is composed of five generations of half-sib progeny with complete phenotypic records produced from controlled infections. To detect the genomic locations of the three distinct phenotypic traits being expressed (innately immune, acquired immune, and immunologically non-responsive), genotypes have been generated for DNA markers ( N=199) spaced at regular intervals (∼20 cm intervals) throughout the entire genome (3000 cm). Although initial ETL detection may be limited by half-sib family size, the unique structure of this population provides additional statistical power for refining map position of potential ETL. After allele frequency and contribution to phenotype are determined in this population, marker tests associated with ETL most beneficial for controlling parasite infection can be accurately used for selection. Comparative map and functional genomic information from humans and other species of biomedical importance will be utilized in further investigations to elucidate the genes underlying ETL.

Role of the bovine immune system and genome in resistance to gastrointestinal nematodes

Role of the bovine immune system and genome in resistance to gastrointestinal nematodes

Dairy cattle genomics: Tools to accelerate genetic improvement?

Traditional selection based on genetic merit calculated from phenotypic and pedigree information has been tremendously effective at improving production in dairy cattle. Hypothetically, genetic improvement could be accelerated even further for yield and other economically important traits by directly selecting upon the genetic differences underlying the phenotypes. To elucidate these genetic differences, research strategies based on genomic science have been developed to identify economic trait loci (ETL). Once resolved with respect to position in the genome, DNA markerbased tests that identify ETL can be practically applied to enhance selection in a commercial setting. To date, most dairy-related ETL have been detected in Holstein grandsire families using the granddaughter design. Because the marker intervals identifying these ETL are not resolved well enough for accurate selection in current populations, ETL analyses have been or are being extended to include ancestral animals that connect family pedigrees and current generations of nonprogenytested animals from within the founder animal pedigree. Increasing genotypic and phenotypic information in this manner alleviates two statistical limitations often associated with ETL interval refinement in experimental populations. First, population size is no longer limited or biased by previous selection. In addition, the inheritance of ETL can be traced from historic families of interest to current generations relevant to the industry. After allele frequency and contribution to phenotype are determined in current populations, those ETL most beneficial for the industry can be accurately used for selection. As an aid to ETL mapping in dairy cattle, efforts have been initiated to catalog as many bovine genes as possible by generating expressed sequence tags (EST) from cDNA clones. These clones represent gene expression at the mRNA level in various tissue types present in cattle. Mapping EST with sequence identity to human genes onto the bovine genetic map is improving the comparative map between species and will aid future investigations in determining genes that underlie ETL. Furthermore, cDNA microarrays constructed with the aid of EST data can be used for hybridization analysis to characterize gene-expression patterns and identify genetic pathways important for animal production and udder health.

Mapping of 16 ESTs expressed in the bovine mammary gland during lactation.

A bovine mammary gland cDNA-library was used to characterize and map genes expressed during lactation. Fifty cDNA clones selected by differential hybridization were sequenced from both ends, and sequences were examined for similarities with database sequences. For 34 of the transcripts, the sequences showed more than 80% similarity to previously characterized genes or expressed sequence tags (ESTs). Twenty cDNAs that could be of interest as candidate genes for milk production are selected for genetic or chromosomal mapping. Twenty-three out of the 39 designed primer pairs representing 16 cDNA clones amplified the expected fragments and were used for subsequent fluorescent single-strand conformation polymorphism analysis (F-SSCP) in the International Bovine Reference Panel families (IBRP). Ten polymorphic loci could be identified and used to genotype the IBRP animals, and nine of them were subsequently genetically mapped on nine chromosomes. In addition, eight loci from the 16 cDNA clones could be mapped by somatic cell hybrids, bringing the total number of mapped genes to 16, one of which was mapped genetically as well as physically. The mapped mammary gland ESTs are potentially useful for cloning economic trait loci by a positional candidate gene cloning approach.

Mapping Economic Trait Loci in Cattle : towards positional cloning of the <<Polled>> locus and dairy QTLs

Mapping Economic Trait Loci in Cattle : towards positional cloning of the <<Polled>> locus and dairy QTLs

Mapping economic trait loci for somatic cell score in Holstein cattle using microsatellite markers and selective genotyping

Marker-assisted selection (MAS) uses genetic marker genotypes to predict an animal's production potential and will provide additional selection information for progeny testing. With the discovery of highly polymorphic microsatellite markers, the tools now exist to begin the search for economic trait loci (ETL), which is the first step toward MAS. The objective of this study was to identify ETL for somatic cell score in an existing Holstein population. Using the granddaughter design, sons from seven grandsire families were genotyped with 20 autosomal microsatellites from five chromosomes (4, 8, 13, 17, 23), with an emphasis on chromosome 23, which is the location of the bovine major histocompatibility complex (BoLA). Selective genotyping was used to reduce the number of genotypes required, in which the 10 highest and 10 lowest sons from the phenotypic distribution curve were tested (140 sons in seven families). One marker (513), located near BoLA, showed evidence of an ETL in three of five polymorphic families. Additional sons were genotyped from the five families to estimate the effect and to compare selective and 'complete' genotyping. Both methods detected an ETL at marker 513, but in different families. This study provides evidence of the usefulness of microsatellite markers and the granddaughter design in the detection of ETL; however, additional markers need to be evaluated to determine the usefulness of selective genotyping. Based on the results from the 20 studied markers, the most likely position of a somatic cell score ETL lies near marker 513, located on chromosome 23.

Prediction of informativeness for microsatellite markers among progeny of sires used for detection of economic trait loci in dairy cattle

Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter design requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.

A genetic and physical map of bovine chromosome 11.

A genetic map of bovine Chromosome (Chr) 11 (BTA11, synteny group U16) has been constructed from 330 animals belonging to 21 families, which constitute the international bovine reference panel (IBRP). This map is based on 13 polymorphic microsatellite markers, two of which were chosen in previously published maps. Three markers have been isolated from cosmids. Two of the three cosmids have been physically localized by fluorescence in situ hybridization (FISH), to anchor the genetic map on the chromosome. In addition, a biallelic polymorphism in the beta-lactoglobulin gene (LGB) has been genetically positioned relative to the microsatellite markers. The most probable order of the markers is: cen-INRA044-BM716-INRA177-(TGLA327, INRA198, INRA131)-INRA111-INRABERN169-(INRA115, INRA032)-INRA108-INRABERN162-INRA195-LGB. The total linkage group spans 126 cM, which probably corresponds to most of the chromosome length. The average intermarker distance is about 10.5 cM, allowing the potential detection of a genetic linkage with any Economic Trait Loci (ETL) of this chromosome. Seven of these markers have been previously published by Vaiman and coworkers (1994), two will be published as part of a set of markers (Eggen et al. in preparation), two are described in this paper, and two (BM716, TGLA327) were chosen from the published maps of BTA11 in order to integrate our data with existing maps. All these markers were assigned to synteny group U16 by use of a previously characterized panel of hamster/bovine somatic hybrid cell lines (Guérin et al. 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

A genetic linkage map for cattle.

We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL).

The Goals and Status of the Bovine Gene Map

The bovine genome map has developed rapidly in recent years. The synteny and chromosomal maps are sufficiently developed to identify chromosomal conservation with other mammals, which is especially useful for the extrapolation of data to cattle from the better developed maps of mouse and human. The rapid development of microsatellite and other hypervariable markers in several laboratories around the world and the availability of a common set of reference families for linkage analysis will produce a 20-cM map in 2 yr. Immediate needs for development are 1) markers to anchor physical maps to linkage maps, 2) resource families segregating economic trait loci, and 3) chromosome-specific libraries to develop densely saturated linkage maps over genomic regions shown to contain economic trait loci.

Bovine Genome Study and Its Goals

The consensus conclusion of several recent major international livestock genetics conferences is that genomic localization of economic trait loci and subsequent marker-assisted selection for these traits will rapidly facilitate genetic improvement of livestock. Genetic improvement of cattle, specifically for efficiency of food utilization, reproductive performance, resistance to disease, and higher quality of beef and dairy products ranks high among the world's agricultural research needs. The necessary tool for large scale improvement of such a diverse array of phenotypes by marker-assisted selection is a 20 centiMorgan map of the bovine genome, consisting of highly polymorphic loci that can be easily scored by teams of investigators studying the segregation of desirable traits. This same map can subsequently be developed to a high level of resolution in regions around genes of particular interest and used to isolate and clone genes involved in the expression of economically important traits.
 Experiments in our laboratory (1, 2, 3) and others (4, 5) demonstrate that the methods that have revolutionized human genetics in the last decade can do the same for cattle genetics. Bovine cells readily hybridize with mouse L cells or hamster E36 cells and segregate cattle chromosomes (1). Genetic analysis of these segregating hybrid cells has produced the current syntenic map of the cow which consists of more than 270 genes including markers of every bovine chromosome. Fifteen of the autosomal syntenic groups have been assigned to chromosomes. Our laboratory has participated in these assignments (6, 7). We have selected genes for physical mapping based on their potential role in key physiological processes and their value in defining the limits of chromosomal conservation with the human and mouse maps. We have used Southern blotting of more than 200 bovine and heterologous probes and more recently, the polymerase chain reaction (PCR) with published primer sequences to generate these maps.