Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies.

"Simple" 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between CPNE9 and BRPF1) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient's phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness - rather than lethality issues - may account for the paucity of "simple" interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

[Population data of five STRs from the INTERPOL series in a mestizo population of western Mexico (State of Jalisco)]. / Datos poblacionales de cinco STRs de la serie INTERPOL en una población mestiza del Occidente de México.

INTRODUCTION: Short tandem repeats (STRs) are the DNA polymorphisms most widely used in forensic genetics and parentage testing. Most common series of STRs are those from FBI (CODIS) and from INTERPOL. While there are data related to the first group, no studies are still known in Mexican populations in regard of the INTERPOL set. OBJECTIVE: To describe the genetic characteristics of five INTERPOL STRs and to estimate their main forensic parameters in a population from western Mexico. MATERIAL AND METHODS: Samples from 100 random volunteers from the State of Jalisco were PCR typed for STRs F13B, D2S1338, FESFPS, Penta D and Penta E. RESULTS: Genotype proportions in all five STRs were in agreement with Hardy-Weinberg expectations (p > 0.05). Heterocygosity varied from 0.68 for FESFPS to 0.91 for Penta E markers. Power of discrimination (PD) and exclusion probability (EP) were in the 0.83-0.97 and 0.46-0.75 ranges, respectively. The five combined STRs give a PE > 0.99143 and PD > 0.99999. CONCLUSIONS: These results contribute to establish data bases representative of western Mexico and are useful in DNA forensic and parentage studies.

Five X-chromosome short tandem repeats in a Western Mexican population.

BACKGROUND: X-linked microsatellites represent an efficient complement of autosomal and Y-chromosomal markers in forensic and kinship analysis. METHODS: DXS337 (n=208), DXS101 (n=208), HPRTB (n=206), DXS8377 (n=220), and DXS7423 (n=213) were genotyped in male and female samples from a Western Mexican Mestizo population using singleplex systems and polyacrylamide gel electrophoresis. RESULTS: Genotype distributions did not deviate from Hardy-Weinberg expectations, and pairwise allele combination analysis was consistent with independent segregation for every marker (p>0.05). Allele frequencies were not different by gender. Differences in allele distribution with respect to Caucasian population data (DXS101, HPRTB, DXS8377, DXS7423) seem attributable to the native Mexican component. For the set of five markers, the combined power of discrimination and the probability of exclusion in paternity tests in trios were greater than 0.999. CONCLUSIONS: The present data reveal that the panel of five X-short tandem repeats analyzed is highly informative in forensic identity and parentage studies in Western Mexico.