Human Chromosome 22 sequenced

Rcjohnsen rcjohnsen at
Wed Jan 26 20:09:10 EST 2000

One down: A human chromosome sequenced
J. Travis
in Science News 156:356-357
Dec. 4, 1999

  It's not the biggest, or the smallest, or the one with the most genes. Still,
chromosome 22 will go down in history as the first human chromosome to have
almost its entire DNA sequence revealed to the world.
    Scientists participating in the international effort to decipher the whole
human genome announced this milestone in the Dec. 2 NATURE. The investigators
report that they've determined more than 33 million bases—the chemical building
blocks of DNA—of chromosome 22 and identified at least 545 genes.
    "It's very exciting," says Bruce A. Roe of the University of Oklahoma in
Norman, a leader of the sequencing project. "We've now got one book of the
Encyclopedia Britannica of life.... We know all the words on its pages. We just
have to go back to our dictionary and find out what all those words mean."
    Twenty-two pairs of chromosomes, plus the X and Y chromosomes, carry almost
all of a person's genes. Chromosome 22 ranks as the second smallest, holding
just under 2 percent of all human DNA. It harbors many genes implicated in
human disorders ranging from birth defects to cancers. Several studies have
suggested that chromosome 22 may also contain a gene predisposing people to
    Four DNA-sequencing teams from Washington University School of Medicine in
St. Louis, the University of Oklahoma, the Sanger Centre in Cambridge, England,
and Keio University School of Medicine in Tokyo led the chromosome-22 effort.
While a private firm is sequencing the human genome using a so-called shotgun
strategy (SN: 5/23/98, p. 334), these investigators pursued a more traditional
approach. They took small pieces of DNA whose locations on chromosome-22 were
known and identified which of four possible bases—adenine, cytosine, guanine,
or  thymine exists at each point along the DNA.
    The international human genome project aims for 99.99 percent accuracy.
Claiming less than 1 mistake for every 50,000 bases, the chromosome-22
sequencers say they've beaten that benchmark. "Since this is the first
chromosome being completed, we wanted to set the standard," says Roe.
    He notes that chromosome-22 crossed the finish line first because
scientists working on specific regions overcame their competitiveness and
freely volunteered copies of their regions' DNA to the four sequencing centers.
The centers made the resulting sequence data freely available worldwide. "The
community really worked together," says Roe. "There was a tremendous spirit of
    The ongoing public release of the sequencing data has already resulted in
several published studies on newly identified chromosome-22 genes. Still,
picking out all the genes remains a formidable task. A computer analysis of the
sequence predicted the presence of more than 800 genes, but the software
produces many false positives, warn the scientists. Using more stringent
criteria, they count 545 genes.
    "The real issue is how you find a gene if you know nothing about it. The
problem is that genes don't come with little flags saying, 'I'm a gene,"' notes
Peter Little of Imperial College In London, who wrote a commentary in the same
issue of NATURE.
>From their tally of genes on chromosome 22, the scientists who sequenced it
predict that the human genome contains at least 45,000 genes. Finding all those
genes isn't the ultimate goal, however.
    "Even when you can identify the genes, there's a lot more to be done on
what does a gene do, what does its protein do, and how is it expressed in
different tissues," notes lan Dunham of the Sanger Centre.
    To address some of those questions, biologists must also study the
noncoding DNA that surrounds genes and regulates their activity. "Because we
have the entire [chromosome-22] sequence, we should have all the elements used
to control the expression of its genes," says Dunham.
    Beyond these genes and regulatory regions, about 40 percent of the
chromosome-22 sequence turns out to consist of seemingly useless, repetitive
stretches of DNA, often labeled junk DNA.
    "We don't know what [those sequences] do, if they do anything at all. They
may just be relics of the evolution of the genome says Dunham.
    The investigators haven't sequenced every base on chromosome 22. They've
largely ignored one of its two arms, the much shorter one, because past
research showed that it doesn't contain genes that encode proteins. Like the
short arms of few other chromosomes, it has man copies of genes that code for
the RNA component of ribosomes, the protein-making factories in cells.
   Even the DNA sequence for the long arm of chromosome 22 has 11 gaps ranging
from a few thousand bases to 150,000. Scientists expect to fill in some of
those gaps, especially one thought to contain a gene involved in breast cancer,
but a few may prove very difficult to
sequence.	—J. Travis

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