Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies

Melanie Legrand, Anja Forche, Anna Selmecki, Christine Chan, David T Kirkpatrick, Judith Berman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Haplotype maps (HapMaps) reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP) segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion) has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

Original languageEnglish (US)
Pages (from-to)18-28
Number of pages11
JournalPLoS Genetics
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2008

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aneuploidy
Aneuploidy
Diploidy
Haplotypes
haplotypes
diploidy
Gene Conversion
gene conversion
Candida albicans
gene
organisms
Genetic Recombination
trisomics
Chromosomes
recombination
single nucleotide polymorphism
chromosome
Single Nucleotide Polymorphism
mitotic recombination
Genome

Cite this

Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies. / Legrand, Melanie; Forche, Anja; Selmecki, Anna; Chan, Christine; Kirkpatrick, David T; Berman, Judith.

In: PLoS Genetics, Vol. 4, No. 1, 01.01.2008, p. 18-28.

Research output: Contribution to journalArticle

Legrand, Melanie ; Forche, Anja ; Selmecki, Anna ; Chan, Christine ; Kirkpatrick, David T ; Berman, Judith. / Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies. In: PLoS Genetics. 2008 ; Vol. 4, No. 1. pp. 18-28.
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