ABSTRACT
Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of 98.38%, allowing a single repeat unit difference. In six samples with known repeat expansions, TRGT detected all expansions while also identifying methylation signals and mosaicism and providing finer repeat length resolution than existing methods. Additionally, we released a database with allele sequences and methylation levels for 937,122 TRs across 100 genomes.
ABSTRACT
Reproductive senescence is evident across many mammalian species. An emerging perspective considers components of reproductive senescence as evolutionarily distinct phenomena: fertility senescence and maternal-effect senescence. While fertility senescence is regarded as the ageing of reproductive physiology, maternal-effect senescence pertains to the declining capacity to provision and rear surviving offspring due to age. Both contribute to reproductive failure in utero making it difficult to differentiate between the two prenatally in the wild. We investigated both components in a long-lived mammal with prolonged maternal care through three parameters: calf survival, interbirth interval (IBI) and lactation period. We provide clear evidence for reproductive senescence in a wild population of bottlenose dolphins (Tursiops aduncus) using 34+ years of longitudinal data on 229 adult females and 562 calves. Calf survival decreased with maternal age, and calves with older mothers had lower survival than predicted by birth order, suggesting maternal-effect senescence. Both lactation period and IBIs increased with maternal age, and IBIs increased regardless of calf mortality, indicating interactions between fertility and maternal-effect senescence. Of calves that survived to weaning, last-born calves weaned later than earlier-born calves, evidence of terminal investment, a mitigating strategy given reduced reproductive value caused by either components of reproductive senescence.
