The human genome contains many loci with high incidence of structural mutations, including insertions and deletions of chromosomal segments. This excessive mutability has accelerated evolution and contributed to human disease but has yet to be explained.
Segments of DNA repeated in low-copy numbers (LCRs) have been previously implicated in promoting structural mutability in specific disease-associated loci. Lack of methylation (hypo-methylation) of genomic DNA has been previously associated with high structural mutability in gibbons and in human cancer cells, but the association with structural mutability in the human germline has not been explored.
A recent study carried out by Scientists from
Baylor College of Medicine, Warsaw University of Technology, Poland, and Texas Children's Hospital, Houston, Texas found a similar association between germline hypo-methylation and genomic instability . Specifically, their evolutionary analyses reveal that methylation deserts, the ~1% fraction of the human genome with the lowest methylation in human sperm, harbor a tenfold higher number of structural mutations than genome-wide average. Moreover, the structural mutations in individuals diagnosed with schizophrenia, bipolar disorder, developmental delay, and autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between methylation of genomic DNA, selective structural mutability, evolution, and human disease. Since germline variations are heritable, this has great implication on evolution.
[Click Here to Read the original paper]
Segments of DNA repeated in low-copy numbers (LCRs) have been previously implicated in promoting structural mutability in specific disease-associated loci. Lack of methylation (hypo-methylation) of genomic DNA has been previously associated with high structural mutability in gibbons and in human cancer cells, but the association with structural mutability in the human germline has not been explored.
A recent study carried out by Scientists from
Baylor College of Medicine, Warsaw University of Technology, Poland, and Texas Children's Hospital, Houston, Texas found a similar association between germline hypo-methylation and genomic instability . Specifically, their evolutionary analyses reveal that methylation deserts, the ~1% fraction of the human genome with the lowest methylation in human sperm, harbor a tenfold higher number of structural mutations than genome-wide average. Moreover, the structural mutations in individuals diagnosed with schizophrenia, bipolar disorder, developmental delay, and autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between methylation of genomic DNA, selective structural mutability, evolution, and human disease. Since germline variations are heritable, this has great implication on evolution.
[Click Here to Read the original paper]
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