Significance of linkage disequilibrium heterogeneous patterns in the 21q22.3 region for mapping 21 trisomy individuals.

Recombination patterns can be indirectly inferred by means of linkage disequilibrium (LD) estimates, since LD is negatively correlated with genetic distance. However, LD does not necessarily have absolute correspondence with genetic distance. We estimated LD at 5 loci located in the 21q22.3 region. These STRs (D21S1440, D21S168, D21S1260, D21S1446, and D21S1411) covered 8.81 Mb of the 21q22.3 region. They were genotyped by conventional PCR. Similar size samples previously validated by sequencing were used as a genotyping control. Three hundred and sixty-nine individuals (62 families) living in Guadalajara, Mexico, were included. As an inclusion criterion, each family had a positive paternity test by autosomal markers for the CODIS core loci. Two hundred and thirty phase known haplotypes were identified by familial segregation. Only those haplotypes whose frequency was higher than 4% were taken into account for LD estimation, expressed as Lewontin's D' coefficient and Bonferroni's correction P values. For all 5 loci, the genetic distributions were in agreement with Hardy-Weinberg expectations. Heterozygosity and haplotype diversity were ≥ 0.69 and 99.58%, respectively. D21S1440-D21S168 (4.51 cM) and D21S1446-D21S1411 (4.58 cM) marker haplotype frequencies were significantly different from those expected by random distribution. The remaining haplotypes, including those with minimal inter-distance (D21S1260-D21S1446, 1.44 Mb), did not show LD. The 5 STRs at the 21q22.3 region in this Mexican population showed a non-homogeneous LD pattern, which demonstrates that recombination or linkage should not be assumed solely on the basis of genetic distance.

Molecular characterization of a patient with 3p deletion syndrome and a review of the literature.

3p deletion syndrome is a rare disorder involving developmental delay, dysmorphic physical features, and growth retardation. Molecular mapping of several cases in the literature have identified a critical region on chromosome 3p26. We present a child patient with characteristic features of 3p deletion syndrome and a de novo unbalanced translocation involving chromosomes 3 and 13. Fine mapping of this rearrangement using fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH) revealed an unbalanced abnormality including a 4.5 Mb terminal deletion of chromosome 3p, telomeric to ITPR1 on 3p26.2, which was not previously identified with routine cytogenetic analysis. In addition, these investigations confirmed and refined the boundaries of a 26.5 Mb deletion of chromosome 13. This study confirms the minimal candidate region for 3p deletion syndrome, provides further evidence implicating haploinsufficiency of CNTN4 in the disorder, and demonstrates the utility of high-resolution investigations of rare chromosomal rearrangements.