Linkage Mapping Of Genes Research Articles

A Comparison on Some Interval Mapping Approaches for QTL Detection.

Quantitative trait locus (QTL) analysis is a statistical method that links two types of information such as phenotypic data (trait measurements) and genotypic data (usually molecular markers). There a number of QTL tools have been developed for gene linkage mapping. Standard Interval Mapping (SIM) or Simple Interval Mapping or Interval Mapping (IM), Haley Knott, Extended Haley Knott and Multiple Imputation (IMP) method when the single-QTL is unlinked and Composite Interval Mapping (CIM) is designed to map the genetic linkage for both linked and unlinked genes in the chromosome. Performance of these methods is measured based on calculated LOD score. The QTLs are considered significant above the threshold LOD score 3.0. For backcross-simulated data, the CIM method performs significantly in detecting QTLs compare to other SIM mapping methods. CIM detected three QTLs in chromosome 1 and 4 whereas the other methods were unable to detect any significant marker positions for simulated data. For a real rice dataset, CIM also showed performance considerably in detecting marker positions compared to other four interval mapping methods. CIM finally detected 12 QTL positions while each of the other four SIM methods detected only six positions.

A cellular retinoic acid-binding protein from zebrafish ( Danio rerio): cDNA sequence, phylogenetic analysis, mRNA expression, and gene linkage mapping

We report the sequence of a cDNA clone coding for a cellular retinoic acid-binding protein (CRABP) in zebrafish. The encoded polypeptide is 142 amino acids in length with an estimated molecular mass of 15.8 kDa and a calculated isoelectric point of 5.2. The zebrafish CRABP exhibits highest sequence identity to the pufferfish CRABPIIa (83%) and CRABPIIb (79%), and human CRABPII (74%) than to any other member of the intracellular lipid-binding protein (ILBP) family. A phylogenetic tree for different members of the ILBP multigene family including fatty acid-binding proteins (FABPs), cellular retinol-binding proteins (CRBPs) and CRABPs shows that the cloned zebrafish cDNA encodes a protein that clusters with CRABPs from other species and not with CRBPs and FABPs. Reverse-transcription polymerase chain reactions (RT-PCR), using oligonucleotide primers specific to the zebrafish CRABP cDNA made from total RNA of embryos collected at various developmental stages, did not detect the CRABP mRNA until 12 h post-fertilization. In adult zebrafish, CRABP mRNA was detected by RT-PCR in total RNA extracted from muscle, testes and skin, barely detectable in heart, ovary and brain and undetectable in liver, kidney and intestine. Quantitative RT-PCR (qRT-PCR) revealed a similar tissue-specific distribution for zebrafish CRABP mRNA with highest levels of CRABP mRNA in muscle followed by testes, skin, ovary and much lower levels in heart. Radiation hybrid mapping assigned the CRABP gene to linkage group 16 in the zebrafish genome. Comparison of the mapped zebrafish CRABP and human CRABPII genes revealed that zebrafish linkage group 16 has a syntenic relationship with human chromosome 1. Based on phylogenetic analysis and the syntenic relationship to the CRABPII gene in human, the zebrafish cDNA clone appears to code for a type II CRABP.

Elucidation of correspondence between swine chromosome 4 and human chromosome 1 by assigning 27 genes to the ImpRH map, and development of microsatellites in the proximity of 14 genes

Loci affecting swine intramuscular fat content, backfat thickness, carcass weight, and daily weight gain were assigned to regions of swine chromosome (SSC) 4, which were shown to correspond to human chromosome (HSA) 1p22→ q25 by ZOO-FISH, bidirectional chromosome painting, as well as by the linkage map of genes. In order to select candidate genes responsible for the above traits from the human genome database, precise correspondence between SSC4 and HSA1 is a prerequisite. In the present study, 27 genes, PTGFR, GBP1, GBP2, GFI1, GCLM, ABCD3, EXTL2, KCNA3, ADORA3, KCND3, WNT2B, NRAS, SYCP1, PTGFRN, IGSF2, NOTCH2, S100A10, SHC1, SSR2, LMNA, CCT3, CD5L, PEA15, FCER1G, EAT2, DDR2, and LAMB3, located in the HSA1 region corresponding to SSC4 or possibly SSC4, were assigned to the IMpRH map. The alignment of genes from centromere to telomere in the SSC4 q arm is basically conserved in HSA1p22→q25 with the direction from the q arm to the p arm, which is in good agreement with results from linkage mapping. In addition, the present study first demonstrated that WNT2B residing in the middle of the HSA1 region was assigned to SSC18 with a high lod score (> 5), and that at least three intrachromosomal rearrangements occurred in the region in the process of swine and human evolution. PTGFR, and LAMB3 localized at both ends of the HSA1 region were assigned to SSC6 and SSC9, respectively, which is consistent with regional correspondence reported earlier. In the course of the above analysis, microsatellite markers were developed in the proximity of eleven genes localized on SSC4, and three genes on other swine chromosomes.

Approaches to identifying genetic variation for complex phenotypes

Among the most challenging problems human geneticists currently face is how to move from the linkage mapping of genes for complex traits to the identification of genetic variation affecting those traits. In this manuscript, we review a variety of the analytic approaches most recently developed for the fine-mapping and positional cloning of genetic variation for complex phenotypes. These approaches, including multipoint linkage disequilibrium mapping, methods for explaining (in the statistical sense) the evidence for linkage, and combinatorial partitioning, can be quite computationally intensive. We also summarize recent research on rapid screening approaches, given that the number of polymorphisms routinely used in genetic studies is rapidly increasing.

Computational Issues in Mapping Variation Affecting Susceptibility to Complex Disorders: The Chicken and the Egg

Linkage mapping strategies for complex disorders have evolved under a variety of constraints. Some of these constraints reflect the nature of complex disorders and are manifest in limitations on the kinds of data that can be collected, while others were (at least historically) strictly computational. This paper focuses on how computational issues have impacted the design of studies on complex disorders and, conversely, how our study designs have influenced the computational issues that have been addressed. We now have unprecedented computational resources, but also face unprecedented computational and methodological challenges as we move from the linkage mapping of genes influencing susceptibility to complex disorders toward the identification of the actual variation affecting susceptibility to these disorders. The near-term computational and methodological issues we must address will be profoundly influenced by the study designs of the recent past. But future study designs, as well as our investments in computational and methodological research, ought to be developed considering the computational and informatics resources we now have at hand.

Genomic Organization and Expression of the Doublesex-Related Gene Cluster in Vertebrates and Detection of Putative Regulatory Regions for DMRT1

Genes related to the Drosophila melanogaster doublesex and Caenorhabditis elegans mab-3 genes are conserved in human. They are identified by a DNA-binding homology motif, the DM domain, and constitute a gene family (DMRTs). Unlike the invertebrate genes, whose role in the sex-determination process is essentially understood, the function of the different vertebrate DMRT genes is not as clear. Evidence has accumulated for the involvement of DMRT1 in male sex determination and differentiation. DMRT2 (known as terra in zebrafish) seems to be a critical factor for somitogenesis. To contribute to a better understanding of the function of this important gene family, we have analyzed DMRT1, DMRT2, and DMRT3 from the genome model organism Fugu rubripes and the medakafish, a complementary model organism for genetics and functional studies. We found conservation of synteny of human chromosome 9 in F. rubripes and an identical gene cluster organization of the DMRTs in both fish. Although expression analysis and gene linkage mapping in medaka exclude a function for any of the three genes in the primary step of male sex determination, comparison of F. rubripes and human sequences uncovered three putative regulatory regions that might have a role in more downstream events of sex determination and human XY sex reversal.

Linkage mapping of genes encoding bone morphogenetic proteins 1, 4 and 5 in sheep.

Probes: cDNA clones for bovine BMP1, BMP4 and BMP51 were used to develop RFLP markers for use with sheep genomic DNA, in order to map the ovine homologues of these genes on the sheep genetic linkage map.

GenoMap: A distributed system for unifying genotyping and genetic linkage analysis

This paper describes GenoMap, an integrated, parallel/distributed computing software system that aids in large-scale gene linkage mapping studies. This problem requires data from heterogeneous, distributed sources. In addition, the users of the system are researchers spanning a wide range of cultures, and represent a broad range of computing needs. A distributed, heterogeneous solution addresses most of the primary challenges, but presents its own difficulties. The key elements of GenoMap are provided by way of a web-based set of interactive Java applets and applications, as well as a small number of native applications, with automated load-balancing support for sharing computationally intensive tasks among a collection of distributed UNIX workstations. While computationally intensive tasks are supported on the most appropriate systems, users are able to conduct most of their work in familiar MacOS and Windows/PC environments through the use of a Java-enabled web browser. We also describe GenoScape, a C & X-Windows/UNIX native application for robust genotyping of a wide range of electrophoresis gel formats.

Genetic analysis of Père David's x red deer interspecies hybrids.

Interspecies hybrids provide unique opportunities for fundamental genetic analyses and for genetic improvement of farmed deer. We have bred F1 hybrids by artificial insemination of red deer hinds (Cervus elaphus) with semen from Père David's deer (Elaphurus davidianus). The male and female F1 Père David deer x red deer hybrids were fertile and in matings with red deer have produced over 300 viable backcross hybrids. DNA was collected from the backcross progeny as an international reference panel for gene linkage mapping and to investigate associations between segregating species-specific genetic markers and phenotypic traits. We have measured a range of phenotypic traits in the backcross hybrids and red deer. Several traits appear suitable for genetic analysis using mapped genetic markers, including gestation length, growth rate, live weight, head morphometrics, and tail length. Typically these traits show a large difference between Père David's deer and red deer and a high variance in the backcross so that many individuals have a phenotype outside the range observed in red deer.

Linkage mapping of genes for resistance to leaf, stem and stripe rusts and ω-secalins on the short arm of rye chromosome 1R

The genes controlling resistance to three wheat rusts, viz., leaf rust (Lr26), stem rust (Sr31) and stripe or yellow rust (Yr9), and ω-secalins (Sec1), located on the short arm of rye chromosome 1R, were mapped with respect to each other and the centromere. Analysis of 214 seeds (or families derived from them) from testcrosses between a 1BL.1RS/1R heterozygote and 'Chinese Spring' ditelocentric 1BL showed no recombination between the genes for resistance to the three rusts, suggesting very tight linkage or perhaps a single complex locus conferring resistance to the three rusts. The rust resistance genes were located 5.4 ± 1.7 cM from the Sec1 locus, which in turn was located 26.1 ± 4.3 cM from the centromere; the gene order being centromere - Sec1 - Lr26/Sr31/Yr9 - telomere. In a second test-cross, using a different 1BL.1RS translocation which had only stem rust resistance (SrR), the above gene order was confirmed despite a very large proportion of aneuploids (45.8%) among the progeny. Furthermore, a map distance of 16.0 ± 4.8 cM was estimated for SrR and the telomeric heterochromatin (C-band) on 1RS. These results suggest that a very small segment of 1RS chromatin is required to maintain resistance to all three wheat rusts. It should be possible but difficult to separate the rust resistance genes from the secalin gene(s), which are thought to contribute to dough stickiness of wheat-rye translocation lines carrying 1RS.

Linkage mapping of genes controlling endosperm storage proteins in wheat

Linkage mapping of genes controlling endosperm storage proteins in wheat

Linkage mapping of genes controlling endosperm storage proteins in wheat

A translocation mapping procedure was used to map gene-centromere distances for the genes controlling endosperm proteins on the short arm of each of the chromosomes 1A, 1B and 1D in wheat. The genes controlling triplet proteins (tentatively designated Tri-1) were found to be closely linked to the centromere on chromosome arms 1AS and 1DS and loosely linked to the gliadin genes (Gli-1) on the same arms. The Gli-1 genes segregated independently or were very loosely linked to their respective centromeres. The Gli-B1-centromere map distance on 1BS was also estimated using conventional telocentric mapping and the result was similar to that obtained with the translocation mapping. A simple two-step one-dimensional electrophoretic procedure is described which allows the low-molecular-weight (LMW) glutenin subunits to be separated from the gliadin bands, thus facilitating the genetic analysis of these LMW subunits. No recombination was observed between the genes (designated Glu-3) controlling some major LMW glutenin subunits and those controlling gliadins on chromosome arms 1AS and 1DS. However, in a separate experiment, the genes controlling LMW glutenin subunits on 1BS (Glu-B3) showed a low frequency of recombination with the gliadin genes.

Genetic Circularity of the Proteus mirabilis Linkage Map

The T incompatibility group plasmid R394 can mobilize the chromosome of Proteus mirabilis strain PM5006. It transferred relatively large segments, corresponding to at least 20 min on the D plasmid chromosomal map of the organism. The frequency of recombination for a large number of selected markers was nearly constant at 5 X 10(-6) per donor cell and it is concluded that mobilization takes place from a number of chromosomal sites. All recombinants were R+ and displayed all properties of the plasmid. By analysing crosses for co-inheritance frequencies of unselected markers, a number of chromosomal loci were assembled in linear array. Linkage between markers at the ends of this linkage group was established to markers at the respective termini of the existing D plasmid linkage group. This established a composite circular linkage map of genes of the P. mirabilis strain PM5006 chromosome.