Multi-ancestry tandem repeat association study of hair colour using exome-wide sequencing.

Hair colour variation is influenced by hundreds of positions across the human genome but this genetic contribution has only been narrowly explored. Genome-wide association studies identified single nucleotide polymorphisms (SNPs) influencing hair colour but the biology underlying these associations is challenging to interpret. We report 16 tandem repeats (TRs) with effects on different models of hair colour plus two TRs associated with hair colour in diverse ancestry groups. Several of these TRs expand or contract amino acid coding regions of their localized protein such that structure, and by extension function, may be altered. We also demonstrate that independent of SNP variation, these TRs can be used to great an additive polygenic score that predicts darker hair colour. This work adds to the growing body of evidence regarding TR influence on human traits with relatively large and independent effects relative to surrounding SNP variation.

The role of tandem repeat expansions in brain disorders.

The human genome contains numerous genetic polymorphisms contributing to different health and disease outcomes. Tandem repeat (TR) loci are highly polymorphic yet under-investigated in large genomic studies, which has prompted research efforts to identify novel variations and gain a deeper understanding of their role in human biology and disease outcomes. We summarize the current understanding of TRs and their implications for human health and disease, including an overview of the challenges encountered when conducting TR analyses and potential solutions to overcome these challenges. By shedding light on these issues, this article aims to contribute to a better understanding of the impact of TRs on the development of new disease treatments.

Exome-wide tandem repeats confer large effects on subcortical volumes in UK Biobank participants.

The human subcortex is involved in memory and cognition. Structural and functional changes in subcortical regions is implicated in psychiatric conditions. We performed an association study of subcortical volumes using 15,941 tandem repeats (TRs) derived from whole exome sequencing (WES) data in 16,527 unrelated European ancestry participants. We identified 17 loci, most of which were associated with accumbens volume, and nine of which had fine-mapping probability supporting their causal effect on subcortical volume independent of surrounding variation. The most significant association involved NTN1 -[GCGG] N and increased accumbens volume (ß=5.93, P=8.16x10 -9 ). Three exonic TRs had large effects on thalamus volume ( LAT2 -[CATC] N ß=-949, P=3.84x10 -6 and SLC39A4 -[CAG] N ß=-1599, P=2.42x10 -8 ) and pallidum volume ( MCM2 -[AGG] N ß=-404.9, P=147x10 -7 ). These genetic effects were consistent measurements of per-repeat expansion/contraction effects on organism fitness. With 3-dimensional modeling, we reinforced these effects to show that the expanded and contracted LAT2 -[CATC] N repeat causes a frameshift mutation that prevents appropriate protein folding. These TRs also exhibited independent effects on several psychiatric symptoms, including LAT2 -[CATC] N and the tiredness/low energy symptom of depression (ß=0.340, P=0.003). These findings link genetic variation to tractable biology in the brain and relevant psychiatric symptoms. We also chart one pathway for TR prioritization in future complex trait genetic studies.

Development and characterization of species-diagnostic ISSR and SCAR DNA markers for differentiating red maple (Acer rubrum) and silver maple (A. saccharinum).

Red maple (Acer rubrum) and silver maple (A. saccharinum) are sister species that readily hybridize in nature. No genetic or barcoding markers have been tested in these species. The main objective of the present study is to develop and characterize molecular markers for distinguishing A. rubrum and A. saccharinum and to validate the hybridity of A. freemanii derived from their crossings using the ISSR marker system. Thirteen A. rubrum and seven A. saccharinum populations were used. Four ISSR primers including ISSR 5, ISSR 8, ISSR 10, and ISSR UBC 825 were selected to amplify genomic DNA from the two species and their hybrids. Each primer generated at least one species-diagnostic ISSR marker for a total of six. Analysis of A. freemanii collected from North Dakota (USA) confirmed that the genotypes screened were true hybrids between A. rubrum and A. saccharinum. These markers were cloned and sequenced. Successful sequences were converted to SCAR markers using specifically designed primers. Overall, the developed diagnostic and specific ISSR and SCAR markers are useful in the certification of these two maple species and their hybrids. They can be used in tracking the introgression of A. rubrum and A. saccharinum DNA in other hybrid trees or populations.