MANY EXAMPLES OF DISEASES RESULTING FROM CHANGES IN COPY NUMBERS PROBABLY SOMETHING TO DUE WITH EGGS & SPERM

Charles Lee, Ph.D.

This analysis of so-called copy number variation (CNV) has now revealed some startling results.

It would seem the assumption that the DNA of any two humans is 99.9% similar in content and identity no longer holds.

The researchers were astonished to locate 1,447 CNVs in nearly 2,900 genes, the starting "templates" written in the DNA that are used by cells to make the proteins which drive our bodies.

This is a huge, hitherto unrecognised, level of variation between one individual and the next.

"Each one of us has a unique pattern of gains and losses of complete sections of DNA," said Matthew Hurles, of the UK's Wellcome Trust Sanger Institute.

"One of the real surprises of these results was just how much of our DNA varies in copy number. We estimate this to be at least 12% of the genome.

"The copy number variation that researchers had seen before was simply the tip of the iceberg, while the bulk lay submerged, undetected. We now appreciate the immense contribution of this phenomenon to genetic differences between individuals."

Evolving story

The new understanding will change the way in which scientists search for genes involved in disease.


"Many examples of diseases resulting from changes in copy number are emerging," commented Charles Lee, one of the project's leaders from Brigham and Women's Hospital and Harvard Medical School in Boston, US.

"A recent review lists 17 conditions of the nervous system alone - including Parkinson's disease and Alzheimer's disease - that can result from such copy number changes."

Scientists are not sure why the copy variations emerge, but it probably has something to do with the shuffling of genetic material that occurs in the production of eggs and sperm; the process is prone to errors.

As well as aiding the investigation of disease and the development of new drugs, the research will also inform the study of human evolution, which probes genetic variation in modern populations for what it can say about their relationship to ancestral peoples.

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285 of the approximately 3,000 CNVs are already known to be
associated with disease, and copy number variations of some of
these genes have been or are now being speculated as risk
factors for ailments such as AIDS, inflammatory bowel disease, lupus, cataracts, arterial disease and
schizophrenia.
One interesting observation that the researchers made during this study was that many of the CNVs have
population-specific characteristics and frequencies, which could explain increased prevalence of some diseases in
certain populations. For example, previous research found that the deletion of the UGT2B17 gene may lead to an
increased risk of prostate cancer in African American men. As a result of this and other research, the consortium is
expanding their studies to thousands of healthy individuals from populations outside of the HapMap collection.