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“Harnessing Linkage Disequilibrium for Mapping Traits: Association Mapping”

 

  Phenotypic selection in crop improvement faces challenges from complex genomic and environmental interactions, limiting expected genetic gains. DNA markers offer effective solutions, standing in for phenotypic traits. Marker-assisted selection requires establishing marker-trait associations through linkage disequilibrium (LD) – non-random allele associations across loci. Two approaches achieve this: family-based mapping exploits transient LD, while association mapping taps historical LD. The latter employs diverse panels like natural populations, germplasm collections, or multi-parent crosses, offering high mapping resolution (up to 1cM or less) to identify the major alleles effectively. For minor alleles, family-based mapping approaches are suitable2.

Association mapping includes two approaches: candidate gene association mapping and genome-wide association mapping. Candidate gene mapping focuses on specific genomic regions guided by prior knowledge, whereas genome-wide mapping is used when gene/QTL positions are unknown2. Fundamentally, these mapping approaches are statistical tools to detect regions co-segregating with markers placed in the genome. Regression of markers as cause and phenotype as effect are widely employed. Generalized linear models and mixed models are used in the absence and presence of population structure and kinship, respectively.

In a study of 496 barley samples, zinc and iron content were assessed. Genome-wide association studies identified 62 SNPs for iron and 68 SNPs for zinc content (initial p < 0.001). Post Bonferroni correction (p < 0.005), 12 SNPs correlated with zinc and 6 with iron. SNP annotations revealed proteins related to transport and nutrient remobilization. These findings pave the way for biofortified barley using marker-assisted selection (MAS) to combat mineral malnutrition3. Using 307 markers (254 cgSSRs, candidate gene based SSRs and 53 rSSRs, random SSRs), a study explored thousand-grain weight genetics in 189 rice genotypes, finding 28 important marker-trait associations. Notably, 23 of the 28 markers were cgSSRs, highlighting their efficiency in identifying genomic regions for quantitative traits in breeding. Gene-based markers like cgSSRs were also effective in improving the accuracy of genomic selection within plant breeding programs1.

Association mapping being an alternative approach to linkage mapping has the advantages of a greater number of alleles detected, fine mapping, less time requirement, etc. However, family mapping approach is effective in capturing minor alleles with major effects. Thus, for an effective crop improvement strategy, AM along with family-based approaches in validating the findings is a good collaboration in evading false positives and truly validating the marker effects.

References:

1. ANILKUMAR, C., MUHAMMED AZHARUDHEEN, T.P., SAH, R.P., SUNITHA, N.C., DEVANNA, B.N., MARNDI, B.C. AND PATRA, B.C., 2023, Gene based markers improve precision of genome-wide association studies and accuracy of genomic predictions in rice breeding. Heredity, 130(5):335-345.

2. CROWELL, S., KORNILIE, P., FALCA, A., ISMAIL, A., GREGORIO, G., MEZEY, J. AND MCCOUCH, S., 2015, Genome-wide association and high-resolution phenotyping link Oryza sativa panicle traits to numerous trait-specific QTL clusters. Nat. Commun., 7:1-14.

 3. NYIRAGUHIRWA, S., GRANA, Z., OUABBOU, H., IRAQI, D., IBRIZ, M., MAMIDI, S. AND UDUPA, S.M., 2022. A genome-wide association study identifying single-nucleotide polymorphisms for iron and zinc biofortification in a worldwide barley collection. Plants, 1(10):1349.

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