Skip to main content
Premium Trial:

Request an Annual Quote

Science Papers Find Single Error Can Lead to Complex Cancer, Ways to Estimate Genotype-Phenotype Associations

A single cell division error can trigger a mutational cascade that leads to the extreme genomic complexity and continually evolving subclonal heterogeneity that characterize cancer, according to a new study in Science. While the extensive chromosomal rearrangements found in cancer genomes can develop gradually, they are also believed to sometimes occur rapidly through various mutational events including the chromosome breakage-fusion-bridge (BFB) cycle, which begins with the formation of an abnormal nuclear structure called a chromosome bridge, and chromothripsis, which is the extensive rearrangement of one or a few chromosomes. To explore a possible mechanistic relationship between these events, a team led by Harvard University scientists recreated the BFB cycle in cultured cells and used single-cell whole-genome sequencing and other techniques to observe the downstream genetic consequences. They show that chromothripsis accumulates through a cascade of mutational events initiated by the aberrant formation of a chromosome bridge, leading to rapid and extensive DNA damage. GenomeWeb has more on this, here.

A review of strategies for estimating genotype-phenotype associations in samples of unrelated individuals, and the population phenomena that can bias such estimates, is presented in Science Advances this week. While heritability, genetic correlation, and genetic associations estimated from samples of unrelated individuals are often perceived as confirmation that genotype causes a phenotype, these estimates can arise from indirect mechanisms due to population phenomena, researchers from the University of Bristol write. Such phenomena include population stratification, dynastic effects, and assortative mating. The scientists highlight this issue with empirical examples focused on socioeconomic phenotypes, suggest tools for detecting these biases, and discuss some potential consequences of and solutions to them.