Results for “Short-tandem repeat (STR)”

PubMed2024

Sequencing the orthologs of human autosomal forensic short tandem repeats provides individual- and species-level identification in African great apes.

BACKGROUND: Great apes are a global conservation concern, with anthropogenic pressures threatening their survival. Genetic analysis can be used to assess the effects of reduced population sizes and the effectiveness of conservation measures. In humans, autosomal short tandem repeats (aSTRs) are widely used in population genetics and for forensic individual identification and kinship testing. Traditionally, genotyping is length-based via capillary electrophoresis (CE), but there is an increasing move to direct analysis by massively parallel sequencing (MPS). An example is the ForenSeq DNA Signature Prep Kit, which amplifies multiple loci including 27 aSTRs, prior to sequencing via Illumina technology. Here we assess the applicability of this human-based kit in African great apes. We ask whether cross-species genotyping of the orthologs of these loci can provide both individual and (sub)species identification. RESULTS: The ForenSeq kit was used to amplify and sequence aSTRs in 52 individuals (14 chimpanzees; 4 bonobos; 16 western lowland, 6 eastern lowland, and 12 mountain gorillas). The orthologs of 24/27 human aSTRs amplified across species, and a core set of thirteen loci could be genotyped in all individuals. Genotypes were individually and (sub)species identifying. Both allelic diversity and the power to discriminate (sub)species were greater when considering STR sequences rather than allele lengths. Comparing human and African great-ape STR sequences with an orangutan outgroup showed general conservation of repeat types and allele size ranges. Variation in repeat array structures and a weak relationship with the known phylogeny suggests stochastic origins of mutations giving rise to diverse imperfect repeat arrays. Interruptions within long repeat arrays in African great apes do not appear to reduce allelic diversity. CONCLUSIONS: Orthologs of most human aSTRs in the ForenSeq DNA Signature Prep Kit can be analysed in African great apes. Primer redesign would reduce observed variability in amplification across some loci. MPS of the orthologs of human loci provides better resolution for both individual and (sub)species identification in great apes than standard CE-based approaches, and has the further advantage that there is no need to limit the number and size ranges of analysed loci.

Animals↗

PubMed2025

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. Although most reported variants are found in protein-coding regions or adjacent junctions, structural variations (SVs) within non-coding regions have not been previously reported. METHODS: We investigated two male siblings with severe neurodevelopmental disorders and spasticity, who had remained undiagnosed for over a decade and were negative from exome sequencing, utilizing long-read HiFi genome sequencing. We conducted a comprehensive analysis including short-tandem repeats (STRs) and SVs to identify the genetic cause in this familial case. RESULTS: While coding variant and STR analyses yielded negative results, SV analysis revealed a novel hemizygous deletion in intron 1 of the SLC16A2 gene (chrX:74,460,691 - 74,463,566; 2,876 bp), inherited from their carrier mother and shared by the siblings. Determination of the breakpoints indicates that the deletion probably resulted from Alu/Alu-mediated rearrangements between homologous AluY pairs. The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process, as well as a regulatory element including an eQTL (rs1263181) that is implicated in the tissue-specific regulation of SLC16A2 expression, notably in skeletal muscle and thyroid tissues. CONCLUSIONS: This report, to our knowledge, is the first to describe a non-coding deletion associated with AHDS, demonstrating the potential utility of long-read sequencing for undiagnosed patients. Although interpreting variants in non-coding regions remains challenging, our study highlights this region as a high priority for future investigation and functional studies.

Humans↗