Dr. Pille Hallast is a Research Scientist at The Jackson Laboratory for Genomic Medicine (USA), where she studies genome diversity and the structure and evolution of the Y chromosome, with a particular interest in how genetic variation in complex genomic regions influences genome function, human health, and reproduction. She completed her undergraduate, master’s, and doctoral training at the University of Tartu, where her early work focused on segmentally duplicated gene clusters involved in human reproduction and their evolution in primates.
Her subsequent research has centred on the Y chromosome as both a marker of human demographic history and a model for studying mutational processes in structurally complex regions of the genome. As a postdoctoral researcher at the University of Leicester and later at the University of Tartu and the Wellcome Sanger Institute, she contributed to some of the first population-scale resequencing studies of the Y chromosome, revealing high rates of gene conversion, new patterns of global diversity, and links between Y-chromosomal variation and human disease and male infertility.
More recently, she has applied long-read sequencing and de novo assembly approaches to resolve previously inaccessible regions of the genome. She is a co-author of the first complete human Y chromosome assemblies, published in Nature in 2023, and is actively involved in the Human Structural Variation Consortium, which aims to improve the detection and characterisation of structural variants and complex genomic regions in diverse human populations.
Why the Y? Long-read assemblies and new insights into diversity and mutation in complex genomic regions
The human Y chromosome is both a powerful marker of human history and one of the most challenging regions of the genome to assemble and interpret. Rich in palindromes, segmental duplications, multicopy gene families, and satellite-rich heterochromatin, it contains complex genomic regions that remained poorly resolved in the era of short-read sequencing. Recent advances in long-read sequencing now make it possible to assemble these regions at near-complete resolution and to study their diversity at population scale.
In this talk, I will discuss how long-read assemblies are changing our view of the Y chromosome and what the Y can teach us more broadly about genome biology. Using examples from recent population-scale Y-chromosome assemblies, I will highlight new insights into structural variation, mutation, and repeat organization across some of the most difficult parts of the genome. These studies show that variation in complex regions can be extensive, but also structured, with recurrent changes often following a limited set of patterns shaped by local sequence architecture. More broadly, the Y chromosome provides a useful model for understanding how repeat-rich regions evolve, how structural mutations arise, and why complete haplotype-resolved assemblies are essential for interpreting genomic diversity. Long-read and pangenome approaches are therefore not only improving representation of the Y chromosome itself, but also helping to define how complex regions of the human genome should be studied in the future.