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. 2011 Jun 1;1(1):3-9.
doi: 10.1534/g3.111.000190.

An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

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Free PMC article

An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

Kevin M Bradley et al. G3 (Bethesda). .
Free PMC article

Abstract

A surprising diversity of mechanisms controls sex determination of vertebrate organisms, even among closely related species. Both genetic and temperature-dependent systems of sex determination have been described in teleost fish. In the common zebrafish model organism, heteromorphic sex chromosomes are not observed, and the potential role of a genetic component of sex determination remains largely unknown. Here we report a genome-wide linkage study of sex determination in zebrafish using a novel SNP genetic map. We identified loci on zebrafish chromosomes 5 (LOD score 7.9) and 16 (LOD score 9.3) governing sex determination as a complex trait, rather than as an XY or ZW genetic system. Each of these loci contains a prominent candidate gene with a conserved role in sex determination across additional species that suggest potential mechanisms of sex determination in zebrafish. The chromosome 5 locus harbors dmrt1, a key gene in sex determination from fruit flies to humans; mutation of the human DMRT1 ortholog is a cause of complete sex reversal of XY individuals. The chromosome 16 locus harbors cyp21a2; mutation of the human CYP21A2 ortholog is one of the more common causes of pseudohermaphroditism. Mutation detection at each of these candidate genes within the zebrafish cross identified hypomorphic variants on the female-associated allele of each locus. The two loci together accounted for 16% of variance of the trait. Interacting environmental cues are likely to be an additional important component of sex determination in zebrafish.

Figures

Figure 1
Figure 1
Unified SNP and STR genetic map of the zebrafish. The SNP map is comprised of 870 SNPs at 618 unique loci (blue tick marks) with a mean locus density of 3.4 Kosambi cM and resolution of 0.01 cM. The SNP genotype data were merged with data of 1989 STRs (red tick marks) of the MGH genetic map for creation of a combined map. The merged map is comprised of 1103 unique loci with a mean locus density of 2.0 Kosambi cM. Further detail of map markers and positions is provided in Table S1.
Figure 2
Figure 2
Recombination rate across the zebrafish genome.
Figure 3
Figure 3
Multipoint interval mapping of sex determination in zebrafish. LOD score results are plotted as a function of marker location in cM, with chromosomal number designated at the bottom of the plot. Dashed horizontal lines indicate significance thresholds (α) determined by permutation testing.
Figure 4
Figure 4
Plot of the proportion of male progeny of the cross as a function of the alleles at the two major sex-determining loci in zebrafish. The B allele of chromosome 5 (originating from the IN strain male grandparent) corresponds to the male-associated allele of dmrt1, here marked by ss48808156 (T variant of the A/T SNP) in the cross. The A allele of chromosome 16 (originating from the AB strain female grandparent) corresponds to the male-associated allele of cyp21a2, here marked by ss48940970 (T variant of the T/C SNP) in the cross. The 95% confidence intervals of the proportion of males among zebrafish with a given two-locus genotype are illustrated for each data point.

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