Biology subjects

Martin, T.

Publications and source records attributed to Martin, T..

3 recordsLinked to original sources

bioRxiv2018

Refined detection and phasing of structural aberrations in pediatric acute lymphoblastic leukemia by linked-read whole genome sequencing

Structural chromosomal rearrangements that may lead to in-frame gene-fusions represent a leading source of information for diagnosis, risk stratification, and prognosis in pediatric acute lymphoblastic leukemia (ALL). However, short-read whole genome sequencing (WGS) technologies struggle to accurately identify and phase such large-scale chromosomal aberrations in cancer genomes. We therefore evaluated linked-read WGS for detection of chromosomal rearrangements in an ALL cell line (REH) and primary samples of varying DNA quality from 12 patients diagnosed with ALL. We assessed the effect of input DNA quality on phased haplotype block size and the detectability of copy number aberrations (CNAs) and structural variants (SVs). Biobanked DNA isolated by standard column-based extraction methods was sufficient to detect chromosomal rearrangements even at low 10x sequencing coverage. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements and aneuploidy assessment. With use of haplotype information from the linked-reads, we also identified additional structural variants, such as a compound heterozygous deletion of ERG in a patient with the DUX4-IGH fusion gene. Thus, linked-read WGS allows detection of important pathogenic variants in ALL genomes at a resolution beyond that of traditional karyotyping or short-read WGS.

genomics↗

bioRxiv2018

New Evidence of the Earliest Domestic Dogs in the Americas

The domestication of dogs probably occurred in Eurasia by 16,000 years ago, with the initial peopling of the Americas potentially happening around the same time. Dogs were long thought to have accompanied the first migrations into the Americas, but conclusive evidence for Paleoindian dogs is lacking. The direct dating of two dogs from the Koster site (Greene Co., Illinois) and a newly-described dog from the Stilwell II site (Pike Co., Illinois) to between 10,190-9,630 cal BP represents the earliest evidence of domestic dogs in the Americas and individual dog burials in worldwide archaeological record. The over 4,500 year discrepancy between the timing of initial human migration into the Americas and the earliest evidence for domesticated dogs suggests either earlier dogs are going unseen or unidentified or dogs arrived later with a subsequent human migration.

paleontology↗

bioRxiv2017

Genetic control of age-related gene expression and complex traits in the human brain

Age is the primary risk factor for many of the most common human diseases--particularly neurodegenerative diseases--yet we currently have a very limited understanding of how each individuals genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimers disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.

genetics↗