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Allen, N. M.

Publications and source records attributed to Allen, N. M..

2 recordsLinked to original sources

The contemporary Pacific gray whale (Eschrichtius robustus) gene pool includes ancestry from a potential ghost population: inferences from population genomics

Local extirpations and extreme bottlenecks can deplete genetic variation and obscure population dynamics, especially in highly mobile species. The gray whale (Eschrichtius robustus) undertakes some of the longest known migrations among mammals, and conventional wisdom acknowledges two stocks (eastern and western gray whales) in the Pacific. Commercial whaling depleted both stocks, and while the Eastern North Pacific (ENP) stock has rebounded, the western stock was feared extirpated. In the post-whaling era, the origin of a small summer aggregation near Sakhalin Island, Russia (which we refer to as the Western North Pacific (WNP) stock) is unclear; this group may include descendants from the original western stock, founders from the eastern stock, or some combination of the two. To clarify the genetic affinities of WNP gray whales, we generated whole genome resequencing data for 74 individuals sampled from both geographic regions to assess their origins. Surprisingly, WNP whales are more genetically varied than ENP whales according to principal components and admixture analyses. We present evidence that this structure is due to mixed ancestry in WNP, with admixture occurring between historical eastern and western stocks. Genomic signals based on both single nucleotide polymorphisms and on copy number variants indicate that despite mixed ancestry, the influx of eastern gene flow has largely homogenized genomic diversity across the Pacific. These findings highlight the ability of whole-genome data to help resolve questions of extirpation and to clarify complex gene flow dynamics in highly mobile species.

genomics↗

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay and seizures. To date, clinical features have been described for eleven patients with (likely) pathogenic SETD1B sequence variants. We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Interestingly, males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Finally, despite the possibility of non-redundant contributions of SETD1B and its paralogue SETD1A to epigenetic control, the clinical phenotypes of the related disorders share many similarities, indicating that elucidating shared and divergent downstream targets of both genes will help to understand the mechanism leading to the neurobehavioral phenotypes. Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

genetics↗