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Targeted Recombinant Progeny: a design for ultra-high resolution mapping of Quantitative Trait Loci in crosses between inbred or pure lines.

Heifetz EM, Soller M - BMC Genet. (2015)

Bottom Line: In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect.Thus even in the presence of polygenic variation, the TRP can still provide major savings.Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,.

View Article: PubMed Central - PubMed

Affiliation: JCT - , Lev Academic Center, 21 Havaad Haleumi, Jerusalem, Israel. eliyahu100@gmail.com.

ABSTRACT

Background: High-resolution mapping of the loci (QTN) responsible for genetic variation in quantitative traits is essential for positional cloning of candidate genes, and for effective marker assisted selection. The confidence interval (QTL) flanking the point estimate of QTN-location is proportional to the number of individuals in the mapping population carrying chromosomes recombinant in the given interval. Consequently, many designs for high resolution QTN mapping are based on increasing the proportion of recombinants in the mapping population. The "Targeted Recombinant Progeny" (TRP) design is a new design for high resolution mapping of a target QTN in crosses between pure, or inbred lines. It is a three-generation procedure generating a large number of recombinant individuals within a QTL previously shown to contain a QTN. This is achieved by having individuals that carry chromosomes recombinant across the target QTL interval as parents of a large mapping population; most of whom will therefore carry recombinant chromosomes targeted to the given QTL. The TRP design is particularly useful for high resolution mapping of QTN that differentiate inbred or pure lines, and hence are not amenable to high resolution mapping by genome-wide association tests.

Results: In the absence of residual polygenic variation, population sizes required for achieving given mapping resolution by the TRP-F2 design relative to a standard F2 design ranged from 0.289 for a QTN with standardized allele substitution effect = 0.2, mapped to an initial QTL of 0.2 Morgan to 0.041 for equivalent QTN mapped to an initial QTL of 0.02 M. In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect. Thus even in the presence of polygenic variation, the TRP can still provide major savings. Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,.

Conclusions: The TRP design can be an effective procedure for achieving high and ultra-high mapping resolution of a target QTN previously mapped to a known confidence interval (QTL).

No MeSH data available.


Related in: MedlinePlus

Construction of a TRP mapping population. We assume a QTN mapped to a known confidence interval bounded by markers MU and MD. Construction of the TRP mapping population begins with one or more G1 individuals heterozygous for alternative alleles at the QTN and for a large series of markers spanning the interval from MU to MD. The G1 individuals are selfed, generating a G2 population. The G2 population is genotyped for the markers MU and MD identifying a subset of individuals (the G2R population) that carry a recombinant chromosome in this region together with one of the parental haplotypes . The G2R individuals are genotyped for the full set of internal markers, identifying the point of recombination of their recombinant chromosome. They are selfed in turn to generate the G3 population. The G3 individuals are genotyped for one of the markers heterozygous in their G2R parent to identify the haplotypes transmitted by the G2R parent. G3 individuals carrying one or two recombinant haplotypes (75% of the total) form the G3R mapping population. Non-recombinant G3 individuals that carry only parental type haplotypes serve to correct for polygenic family effects
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Fig1: Construction of a TRP mapping population. We assume a QTN mapped to a known confidence interval bounded by markers MU and MD. Construction of the TRP mapping population begins with one or more G1 individuals heterozygous for alternative alleles at the QTN and for a large series of markers spanning the interval from MU to MD. The G1 individuals are selfed, generating a G2 population. The G2 population is genotyped for the markers MU and MD identifying a subset of individuals (the G2R population) that carry a recombinant chromosome in this region together with one of the parental haplotypes . The G2R individuals are genotyped for the full set of internal markers, identifying the point of recombination of their recombinant chromosome. They are selfed in turn to generate the G3 population. The G3 individuals are genotyped for one of the markers heterozygous in their G2R parent to identify the haplotypes transmitted by the G2R parent. G3 individuals carrying one or two recombinant haplotypes (75% of the total) form the G3R mapping population. Non-recombinant G3 individuals that carry only parental type haplotypes serve to correct for polygenic family effects

Mentions: It is convenient to describe the TRP by starting with an F1 generation created by crossing two pure lines homozygous for alternative alleles at a large number of marker loci and at the target QTL. However, the TRP can equally be initiated from any population (denoted the G1 generation), with a similar F1-type genetic structure. On the basis of previous mapping studies, these G1 individuals will have genotypes of known haplotype composition, including phase of the QTN allele. By appropriate notation of marker and QTN alleles, these genotypes can be given the form: MU-Q--MD/mU-q--mD, where MU and MD are markers defining the upstream (MU) and downstream (MD) (1-α) CI boundaries of the original QTL of width C M (see Figure 1). Q and q are alternative alleles at the QTN, and a large number of markers with alternative alleles (not shown) are found spanning the region between MU and MD.Figure 1


Targeted Recombinant Progeny: a design for ultra-high resolution mapping of Quantitative Trait Loci in crosses between inbred or pure lines.

Heifetz EM, Soller M - BMC Genet. (2015)

Construction of a TRP mapping population. We assume a QTN mapped to a known confidence interval bounded by markers MU and MD. Construction of the TRP mapping population begins with one or more G1 individuals heterozygous for alternative alleles at the QTN and for a large series of markers spanning the interval from MU to MD. The G1 individuals are selfed, generating a G2 population. The G2 population is genotyped for the markers MU and MD identifying a subset of individuals (the G2R population) that carry a recombinant chromosome in this region together with one of the parental haplotypes . The G2R individuals are genotyped for the full set of internal markers, identifying the point of recombination of their recombinant chromosome. They are selfed in turn to generate the G3 population. The G3 individuals are genotyped for one of the markers heterozygous in their G2R parent to identify the haplotypes transmitted by the G2R parent. G3 individuals carrying one or two recombinant haplotypes (75% of the total) form the G3R mapping population. Non-recombinant G3 individuals that carry only parental type haplotypes serve to correct for polygenic family effects
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4492090&req=5

Fig1: Construction of a TRP mapping population. We assume a QTN mapped to a known confidence interval bounded by markers MU and MD. Construction of the TRP mapping population begins with one or more G1 individuals heterozygous for alternative alleles at the QTN and for a large series of markers spanning the interval from MU to MD. The G1 individuals are selfed, generating a G2 population. The G2 population is genotyped for the markers MU and MD identifying a subset of individuals (the G2R population) that carry a recombinant chromosome in this region together with one of the parental haplotypes . The G2R individuals are genotyped for the full set of internal markers, identifying the point of recombination of their recombinant chromosome. They are selfed in turn to generate the G3 population. The G3 individuals are genotyped for one of the markers heterozygous in their G2R parent to identify the haplotypes transmitted by the G2R parent. G3 individuals carrying one or two recombinant haplotypes (75% of the total) form the G3R mapping population. Non-recombinant G3 individuals that carry only parental type haplotypes serve to correct for polygenic family effects
Mentions: It is convenient to describe the TRP by starting with an F1 generation created by crossing two pure lines homozygous for alternative alleles at a large number of marker loci and at the target QTL. However, the TRP can equally be initiated from any population (denoted the G1 generation), with a similar F1-type genetic structure. On the basis of previous mapping studies, these G1 individuals will have genotypes of known haplotype composition, including phase of the QTN allele. By appropriate notation of marker and QTN alleles, these genotypes can be given the form: MU-Q--MD/mU-q--mD, where MU and MD are markers defining the upstream (MU) and downstream (MD) (1-α) CI boundaries of the original QTL of width C M (see Figure 1). Q and q are alternative alleles at the QTN, and a large number of markers with alternative alleles (not shown) are found spanning the region between MU and MD.Figure 1

Bottom Line: In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect.Thus even in the presence of polygenic variation, the TRP can still provide major savings.Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,.

View Article: PubMed Central - PubMed

Affiliation: JCT - , Lev Academic Center, 21 Havaad Haleumi, Jerusalem, Israel. eliyahu100@gmail.com.

ABSTRACT

Background: High-resolution mapping of the loci (QTN) responsible for genetic variation in quantitative traits is essential for positional cloning of candidate genes, and for effective marker assisted selection. The confidence interval (QTL) flanking the point estimate of QTN-location is proportional to the number of individuals in the mapping population carrying chromosomes recombinant in the given interval. Consequently, many designs for high resolution QTN mapping are based on increasing the proportion of recombinants in the mapping population. The "Targeted Recombinant Progeny" (TRP) design is a new design for high resolution mapping of a target QTN in crosses between pure, or inbred lines. It is a three-generation procedure generating a large number of recombinant individuals within a QTL previously shown to contain a QTN. This is achieved by having individuals that carry chromosomes recombinant across the target QTL interval as parents of a large mapping population; most of whom will therefore carry recombinant chromosomes targeted to the given QTL. The TRP design is particularly useful for high resolution mapping of QTN that differentiate inbred or pure lines, and hence are not amenable to high resolution mapping by genome-wide association tests.

Results: In the absence of residual polygenic variation, population sizes required for achieving given mapping resolution by the TRP-F2 design relative to a standard F2 design ranged from 0.289 for a QTN with standardized allele substitution effect = 0.2, mapped to an initial QTL of 0.2 Morgan to 0.041 for equivalent QTN mapped to an initial QTL of 0.02 M. In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect. Thus even in the presence of polygenic variation, the TRP can still provide major savings. Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,.

Conclusions: The TRP design can be an effective procedure for achieving high and ultra-high mapping resolution of a target QTN previously mapped to a known confidence interval (QTL).

No MeSH data available.


Related in: MedlinePlus