• 제목/요약/키워드: QTL Fine Mapping

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Evaluation of a Fine-mapping Method Exploiting Linkage Disequilibrium in Livestock Populations: Simulation Study

  • Kim, JongJoo;Farnir, Frederic
    • Asian-Australasian Journal of Animal Sciences
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    • 제19권12호
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    • pp.1702-1705
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    • 2006
  • A simulation study was conducted to evaluate a fine-mapping method exploiting population-wide linkage disequilibrium. Data were simulated according to the pedigree structure based on a large paternal half-sib family population with a total of 1,034 or 2,068 progeny. Twenty autosomes of 100 cM were generated with 5 cM or 1 cM marker intervals for all founder individuals in the pedigree, and marker alleles and a number of quantitative trait loci (QTL) explaining a total of 70% phenotypic variance were generated and randomly assigned across the whole chromosomes, assuming linkage equilibrium between the markers. The founder chromosomes were then descended through the pedigree to the current offspring generation, including recombinants that were generated by recombination between adjacent markers. Power to detect QTL was high for the QTL with at least moderate size, which was more pronounced with larger sample size and denser marker map. However, sample size contributed much more significantly to power to detect QTL than map density to the precise estimate of QTL position. No QTL was detected on the test chromosomes in which QTL was not assigned, which did not allow detection of false positive QTL. For the multiple QTL that were closely located, the estimates of the QTL positions were biased, except when the QTL were located on the right marker positions. Our fine mapping simulation results indicate that construction of dense maps and large sample size is needed to increase power to detect QTL and mapping precision for QTL position.

Current Status of Quantitative Trait Locus Mapping in Livestock Species - Review -

  • Kim, Jong-Joo;Park, Young I.
    • Asian-Australasian Journal of Animal Sciences
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    • 제14권4호
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    • pp.587-596
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    • 2001
  • In the last decade, rapid developments in molecular biotechnology and of genomic tools have enabled the creation of dense linkage maps across whole genomes of human, plant and animals. Successful development and implementation of interval mapping methodologies have allowed detection of the quantitative trait loci (QTL) responsible for economically important traits in experimental and commercial livestock populations. The candidate gene approach can be used in any general population with the availability of a large resource of candidate genes from the human or rodent genomes using comparative maps, and the validated candidate genes can be directly applied to commercial breeds. For the QTL detected from primary genome scans, two incipient fine mapping approaches are applied by generating new recombinants over several generations or utilizing historical recombinants with identity-by-descent (IBD) and linkage disequilibrium (LD) mapping. The high resolution definition of QTL position from fine mapping will allow the more efficient implementation of breeding programs such as marker-assisted selection (MAS) or marker-assisted introgression (MAI), and will provide a route toward cloning the QTL.

Evaluation of a New Fine-mapping Method Exploiting Linkage Disequilibrium: a Case Study Analysing a QTL with Major Effect on Milk Composition on Bovine Chromosome 14

  • Kim, JongJoo;Georges, Michel
    • Asian-Australasian Journal of Animal Sciences
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    • 제15권9호
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    • pp.1250-1256
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    • 2002
  • A novel fine-mapping method exploiting linkage disequilibrium (LD) was applied to better refine the quantitative trait loci (QTL) positions for milk production traits on bovine chromosome 14 in the pedigree comprising 22 paternal half-sib families of a Black-and-White Holstein-Friesian grand-daughter design in the Netherlands for a total of 1,034 sons. The chromosome map was constructed with the 31 genetic markers spanning 90 Kosambi cM with the average inter-marker distance of 3.5 cM. The linkage analyses, in which the effects of sire QTL alleles were assumed random and the random factor of the QTL allelic effects was incorporated into the Animal Model, found the QTL for milk, fat, and protein yield and fat and protein % with the Lod scores of 10.9, 2.3, 6.0, 25.4 and 3.2, respectively. The joint analyses including LD information by use of multi-marker haplotypes highly increased the evidence of the QTL (Lod scores were 25.1, 20.9, 11.0, 85.7 and 17.4 for the corresponding traits, respectively). The joint analyses including DGAT markers in the defined haplotypes again increased the QTL evidence and the most likely QTL positions for the five traits coincided with the position of the DGAT gene, supporting the hypothesis of the direct causal involvement of the DGAT gene. This study strongly indicates that the exploitation of LD information will allow additional gains of power and precision in finding and localising QTL of interest in livestock species, on the condition of high marker density around the QTL region.

Detection of QTL for Carcass Quality on Chromosome 6 by Exploiting Linkage and Linkage Disequilibrium in Hanwoo

  • Lee, J.H.;Li, Y.;Kim, J.J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제25권1호
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    • pp.17-21
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    • 2012
  • The purpose of this study was to improve mapping power and resolution for the QTL influencing carcass quality in Hanwoo, which was previously detected on the bovine chromosome (BTA) 6. A sample of 427 steers were chosen, which were the progeny from 45 Korean proven sires in the Hanwoo Improvement Center, Seosan, Korea. The samples were genotyped with the set of 2,535 SNPs on BTA6 that were imbedded in the Illumina bovine 50 k chip. A linkage disequilibrium variance component mapping (LDVCM) method, which exploited both linkage between sires and their steers and population-wide linkage disequilibrium, was applied to detect QTL for four carcass quality traits. Fifteen QTL were detected at 0.1% comparison-wise level, for which five, three, five, and two QTL were associated with carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area (LMA), and marbling score (Marb), respectively. The number of QTL was greater compared with our previous results, in which twelve QTL for carcass quality were detected on the BTA6 in the same population by applying other linkage disequilibrium mapping approaches. One QTL for LMA was detected on the distal region (110,285,672 to 110,633,096 bp) with the most significant evidence for linkage (p< $10^{-5}$). Another QTL that was detected on the proximal region (33,596,515 to 33,897,434 bp) was pleiotrophic, i.e. influencing CWT, BFT, and LMA. Our results suggest that the LDVCM is a good alternative method for QTL fine-mapping in detection and characterization of QTL.

Challenges for QTL Analysis in Crops

  • Long, Yan;Zhang, Chunyu;Meng, Jinling
    • Journal of Crop Science and Biotechnology
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    • 제11권1호
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    • pp.7-12
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    • 2008
  • Quantitative trait loci, a genetic concept for explaining the inheritance of non-Mendelian traits in 1940s, have been realized as particular fragments of chromosome even unique genes in most crops in 21st century. However, only very a small portion of QTL has been screened out by geneticists comparing to a great number of genes underneath the quantitative traits. These identified QTL even have been seldom used into breeding program because crop breeders may not find the QTL in their breeding populations in their field station. Several key points will be proposed to meet the challenges of QTL analysis today: a fine mapping population and the related reference genetic map, QTL evaluation in multiple environments, recognizing real QTL with small genetic effect, map integration.

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Identification of Candidate Genes Associated with Beef Marbling Using QTL and Pathway Analysis in Hanwoo (Korean Cattle)

  • Park, Hye-Sun;Seo, Seong-Won;Cho, Yong-Min;Oh, Sung-Jong;Seong, Hwan-Hoo;Lee, Seung-Hwan;Lim, Da-Jeong
    • Asian-Australasian Journal of Animal Sciences
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    • 제25권5호
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    • pp.613-620
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    • 2012
  • Marbling from intramuscular fat is an important trait of meat quality and has an economic benefit for the beef industry. Quantitative trait loci (QTL) fine mapping was performed to identify the marbling trait in 266 Hanwoo steers using a 10K single nucleotide polymorphism panel with the combined linkage and linkage disequilibrium method. As a result, we found nine putative QTL regions for marbling: three on BTA6, two on BTA17, two on BTA22, and two on BTA29. We detected candidate genes for marbling within 1 cM of either side of the putative QTL regions. Additionally, to understand the functions of these candidate genes at the molecular level, we conducted a functional categorization using gene ontology and pathway analyses for those genes involved in lipid metabolism or fat deposition. In these putative QTL regions, we found 95 candidate genes for marbling. Using these candidate genes, we found five genes that had a direct interaction with the candidate genes. We also found SCARB1 as a putative candidate gene for marbling that involves fat deposition related to cholesterol transport.

Quantitative Trait Loci Mapping for Porcine Backfat Thickness

  • Wu, X.L.;Lee, C.;Jiang, J.;Peng, Y.L.;Yan, H.F.;Yang, S.L.;Xiao, B.N.;Liu, X.C.;Shi, Q.S.
    • Asian-Australasian Journal of Animal Sciences
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    • 제15권7호
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    • pp.932-937
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    • 2002
  • A partial genome scan using porcine microsatellites was carried out to detect quantitative trait loci (QTL) for backfat thickness (BFT) in a pig reference population. This population carried QTL on chromosomes 1, 13 and 18. The QTL on chromosome 1 was located between marker loci S0113 and SW1301. The QTL corresponded to very low density lipoprotein receptor gene (VLDLR) in location and in biological effects, suggesting that VLDLR might be a candidate gene. The QTL found on chromosome 13 was found between marker loci SWR1941 and SW864, but significance for the marker-trait association was inconsistent by using data with different generations. The QTL on chromosome 18 was discovered between markers S0062 and S0117, and it was in proximity of the regions where IGFBP3 and GHRHR were located. The porcine obese gene might be also a candidate gene for the QTL on chromosome 18. In order to understand genetic architecture of BFT better, fine mapping and positional comparative candidate gene analyses are necessary.

QTL Identification Using Combined Linkage and Linkage Disequilibrium Mapping for Milk Production Traits on BTA6 in Chinese Holstein Population

  • Hu, F.;Liu, J.F.;Zeng, Z.B.;Ding, X.D.;Yin, C.C.;Gong, Y.Z.;Zhang, Q.
    • Asian-Australasian Journal of Animal Sciences
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    • 제23권10호
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    • pp.1261-1267
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    • 2010
  • Milk production traits are important economic traits for dairy cattle. The aim of the present study was to refine the position of previously detected quantitative trait loci (QTL) on bovine chromosome 6 affecting milk production traits in Chinese Holstein dairy cattle. A daughter design with 918 daughters from 8 elite sire families and 14 markers spanning the previously identified QTL region were used in the analysis. We employed a combined linkage and linkage disequilibrium analysis (LDLA) approach with two options for calculating the IBD probabilities, one was based on haplotypes of all 14 markers (named Method 1) and the other based on haplotypes with sliding windows of 5 markers (named Method 2). For milk fat yield, the two methods revealed a highly significant QTL located within a 6.5 cM interval (Method 1) and a 4.0 cM interval (Method 2), respectively. For milk protein yield, a highly significant QTL was detected within a 3.0 cM interval (Method 1) or a 2.5 cM interval (Method 2). These results confirmed the findings of our previous study and other studies, and greatly narrowed down the QTL positions.

Detection of QTL on Bovine X Chromosome by Exploiting Linkage Disequilibrium

  • Kim, Jong-Joo
    • Asian-Australasian Journal of Animal Sciences
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    • 제21권5호
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    • pp.617-623
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    • 2008
  • A fine-mapping method exploiting linkage disequilibrium was used to detect quantitative trait loci (QTL) on the X chromosome affecting milk production, body conformation and productivity traits. The pedigree comprised 22 paternal half-sib families of Black-and-White Holstein bulls in the Netherlands in a grand-daughter design for a total of 955 sons. Twenty-five microsatellite markers were genotyped to construct a linkage map on the chromosome X spanning 170 Haldane cM with an average inter-marker distance of 7.1 cM. A covariance matrix including elements about identical-by-descent probabilities between haplotypes regarding QTL allele effects was incorporated into the animal model, and a restricted maximum-likelihood method was applied for the presence of QTL using the LDVCM program. Significance thresholds were obtained by permuting haplotypes to phenotypes and by using a false discovery rate procedure. Seven QTL responsible for conformation types (teat length, rump width, rear leg set, angularity and fore udder attachment), behavior (temperament) and a mixture of production and health (durable prestation) were detected at the suggestive level. Some QTL affecting teat length, rump width, durable prestation and rear leg set had small numbers of haplotype clusters, which may indicate good classification of alleles for causal genes or markers that are tightly associated with the causal mutation. However, higher maker density is required to better refine the QTL position and to better characterize functionally distinct haplotypes which will provide information to find causal genes for the traits.

Identification of a Novel Bakanae Disease Resistance QTL in Zenith Cultivar Rice (Oryza sativa L.)

  • Sais-Beul Lee;Jun-Hyun Cho;Nkulu Rolly Kabange;Sumin Jo;Ji-Yoon Lee;Yeongho Kwon;Ju-Won Kang;Dongjin Shin;Jong-Hee Lee;You-Cheon Song;Jong-Min Ko;Dong-Soo Park
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2020년도 추계국제학술대회
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    • pp.64-64
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    • 2020
  • Bakanae disease, caused by several Fusarium species, imposes serious limitations to the productivity of rice across the globe. The incidence of this disease has been shown to increase, particularly in major rice-growing countries. Thus, the use of high resistant rice cultivars offers a comparative advantage, such as being cost effective, and could be preferred to the use of fungicides. In this research, we used a tropical japonica rice variety, Zenith, a bakanae disease resistant line selected as donor parent. A RIL population (F8:9) composed of 180 lines generated from a cross between Ilpum and Zenith was used. In primary mapping, a QTL was detected on the short arm of chromosome 1, covering about 3.5 Mb region flanked by RM1331 and RM3530 markers. The resistance QTL, qBK1Z, explained about 30.93% of the total phenotype variation (PVE, logarith of the odds (LOD) of 13.43). Location of qBK1Z was further narrowed down to 730 kb through fine mapping using additional RM markers, including those previously reported and developed by Sid markers. Furthermore, there is a growing need to improving resistance to bakanae disease and promoting breeding efficiency using MAS from qBK1Z region. The new QTL, qBK1Z, developed by the current study is expected to be used as foundation to promoting breeding efficiency with an enhanced resistance against bakanae disease. Moreover, this study provides useful information for developing resistant rice lines carrying single or multiple major QTLs using gene pyramiding approach and marker-assisted breeding.

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