(A) Haplotype determination by chromosomal variation analysis. A typical chromosome pair in C. albicans is depicted in the upper left. One homolog is shown in red, the other in blue, with centromeres indicated as a grey circle. This chromosome pair bears a single nucleotide polymorphism (SNP) on the left arm, shown as a “t” on the red homolog and a “c” on the blue. If this chromosome pair is analyzed (arrow 1), SNP analysis will demonstrate that the two SNP variants are present in a 1:1 ratio, while comparative genome hybridization (CGH) will demonstrate that there are two copies of the entire chromosome. This chromosome pair undergoes an alteration in copy number (arrow 2): simple chromosome loss (2a), loss and homozygosis of the remaining homolog (2b), and duplication of an extra copy of one of the homologs, leading to trisomy (2c). SNP analysis of the chromosome loss event (2a) will show that only one of the two alleles is present, while CGH analysis will indicate a reduction in chromosome number. Analysis of the homozygosis (2b) will give the same SNP result but indicate a diploid chromosome number, while analysis of the trisomy (2c) will show a 1:2 ratio of the SNP alleles and the gain of a third chromosome. These results allow the unambiguous mapping of a particular SNP allele to a particular homolog (designated “a” or “b”).
(B) Allelic fractions can be indicative of heterozygous trisomies of whole chromosomes. Allelic fractions (AF) of SNPs on ChR for strains YJB10699, SC5314, YJB10700, and YJB10698, which served as reference strains for the individual genotypes. Allelic fractions were calculated: AF-allele b + AF-allele a/(AF-allele b + AF-allele a). Ranges for genotype calls: AF<0.4−homozygous allele a; AF>0.4 and <0.6 − heterozygous a/b; AF>0.6−homozygous allele b.
(C) Plot of allelic fractions for SNP loci on ChR in four reference strains. Allelic fractions for strains YJB10699, SC5314, YJB10700, and YJB10698 (x-axis) and the corresponding SNP (y-axis). Allelic fractions for strains YJB10699, SC5314, and YJB10698 fall into the expected ranges. For strain YJB10700, the allelic fractions fall between the heterozygous and homozygous range indicating a possible trisomy.
(D) CGH profiles of ChR for reference strains YJB10699, SC5314, YJB10700, and YJB10698. CGH profiles for ChR for the four reference strains confirm the diploid homozygous state for strains YJB10699 (homozygous a/a) and YJB10698 (homozygous b/b), the heterozygous diploid state for strain SC5314 (a/b), and the trisomic heterozygous state for strain YJB10700 (2× allele a, 1× allele b).

Chromosomes are listed from ChR, Ch1 through Ch7. Homologs are designated as “a” and “b”. Alleles on homolog “a” are indicated in red, while alleles on “b” are indicated in blue. Horizontal numbers are the unique IDs for each SNP locus. Each vertical pair of capital letters indicates the heterozygous nucleotide present at each SNP. Centromeres are indicated as gray ovals. MRS (or RB2 in the case of Ch3) sequences are indicated as black vertical bars on each chromosome.

Chromosomes are listed from ChR, Ch1 through Ch7; homolog names were assigned based on the allele type (“a” or “b”) of the SNPs closest to the centromere in reference to the SC5314 haplotype map in . If chromosomes were homozygous at the centromere, the two different homologs were numbered −1 and −2 (e.g., Ch3a-1 and Ch3a-2). Alleles on homolog “a” are indicated in red, while alleles on “b” are indicated in blue. Numbers displayed horizontally along the chromosomes are the unique IDs for each SNP locus. Each vertical pair of capital letters indicates the heterozygous nucleotide present at each SNP. Centromeres are indicated as gray ovals. MRS (or RB2 in the case of Ch3) sequences are indicated as black vertical bars on each chromosome. Recombination tracts are identified based on rearrangement of alleles compared to strain SC5314. Some SNPs used in the SC5314 map are not present in the T118 map due to technical issues.

A view of the extent of copy number changes plotted across the complete length of Ch1 using chromosome map []. CGH data were ordered along the chromosome as described in Materials and Methods. Data were plotted as log2 values, which correspond to the chromosome copy number indicated on the y-axis.