Projects Give View Of Structural Differences Among Individuals And Find Previous

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Projects Give View Of Structural Differences Among Individuals And

Find Previously Unknown Human DNA

http://www.medicalnewstoday.com/articles/105958.php

A nationwide consortium led by the University of Washington in

Seattle has completed the first sequence-based map of structural

variations in the human genome, giving scientists an overall picture

of the large-scale differences in DNA between individuals. The

project gives researchers a guide for further research into these

structural differences, which are believed to play an important role

in human health and disease. The results appear in the May 1 issue of

the journal Nature.

The project involved sequencing the genomes of eight people from a

diverse set of ethnic backgrounds: four individuals of African

descent, two of Asian descent, and two of European background. The

researchers created what's called a clone map, taking multiple copies

of each of the eight genomes and breaking them into numerous segments

of about 40,000 base pairs, which they then fit back together based

on the human reference genome. They searched for structural

differences that ranged in size from a few thousand to a few million

base pairs. Base pairs are one of the basic units of information on

the human genome.

Most previous studies of the genome have focused on small genetic

variations called SNPs (pronounced " snips " ), or single-nucleotide

polymorphisms -- changes on the scale of a single base pair. More

recent research on the human genome has shown, however, that larger-

scale differences may account for a great deal of genetic variation

among individuals. Structural variation in the human genome has

already been linked to individual differences in susceptibility to

conditions like coronary heart disease, HIV, schizophrenia, autism,

and mental retardation.

In addition to millions of smaller differences, the researchers

identified 1695 regions of structural variation in the genome. They

also provided a detailed look at the sequence for 261 regions of the

genome, revealing an unprecedented view of the complexity of the

genetic differences among different humans. The large-scale

differences that the researchers were looking for can come in many

forms, such as the deletion of a large swath of DNA, or the insertion

of an out-of-place string of genetic code. Others simply appear as a

different number of copies of a gene or DNA sequence.

Until now, there has not been a comprehensive study to sequence these

variations systematically in multiple individuals. As part of their

study, the authors also discovered 525 segments of DNA that were

previously unknown to the human genetics community.

" There is a perception that the human genome is essentially

completely understood, " explained the project's leader, Dr. Evan

Eichler, UW associate professor of genome sciences and an

investigator for the Medical Institute. " The sequences

we have identified range in size from a few thousand to hundreds of

thousands of base pairs, and are not part of the published human

genome reference sequence. We found that many of these are highly

variable in copy and content between individuals. This represents

uncharted territory that can now be examined in more detail to

determine the function of these new segments of the human genome with

respect to disease and gene activity. "

Eichler expects that the structural variation map will give

scientists a much better picture of genetic variations, and help them

better understand these areas of the genome that are prone to large-

scale changes over time. Even more research is needed on structural

variations, the scientists argue in the article, to help get a more

accurate picture of the human genome than what we already have in the

reference genome constructed by the Human Genome Project.

" The important point here is that we could not have found these

differences without sequencing more human genomes from individuals of

diverse ancestry to a high-quality standard, " Eichler added.

The project will also serve as a sound resource for the science

community, said Eichler, since the researchers have preserved the

many segments of DNA used for the project. As new genomes are

studied, someone might find a new sequence or new area of variation,

and the researchers can revisit that particular segment of DNA to

study it more closely.