送交者: Latino2 于 October 25, 2004 14:53:28:
Down Syndrome, 旧称蒙古症，是染色体异常里最常见的，大部分蒙
古症患者为21 号染色体三体， 发生率在１／７００左右。
原来以蒙古症是由 21 号染色体上约少数“关键基因”引起的。最新实验表明：蒙
古症的病因并非原来想像的那么简单。
这项实验先培育出带有一份， 两份， 和三份拷贝“关键基因”的老鼠，检测其
是否表现“蒙古症”。结果发现， 拥有三份拷贝“关键基因”的老鼠表型正常。
并没有眼睛外斜，鼻梁塌陷，弱智等症状，说明这些“关键基因”的重复并非唐氏
综合症的根本原因。 科学家认为很可能有更多的基因涉及唐氏综合症的发生。
这项发现也使原来用基因疗法治疗“蒙古症”的设想成为泡影。
Key genes may not create Down syndrome
Paula Gould
The small group of genes long believed to cause Down syndrome are unlikely
to be the real culprits, according to recent research in mice. The finding
is bad news for those devising therapeutic strategies, whose job would be
simplified if blame could be laid at the door of just a few genes.
Down syndrome occurs in around 1 in 700 live births. The vast majority of
people with the condition are born with three complete copies of chromosome
21 instead of two. But a small proportion of individuals with Down syndrome
have only certain portions of chromosome 21 in triplicate.
Although chromosome 21 contains over 200 genes, comparison of people with
complete and partial repetition led researchers to believe that most features
of Down syndrome are caused by a so-called 'critical region' of chromosome
21, which contains just 30 or so genes. This idea has held sway for the past
30 years.
The very simplistic explanation we had before was wrong.
Now researchers have used genetically engineered mice to disprove the theory.
They bred mice with one, two and three copies of the mouse equivalents
of genes from the critical region of human chromosome 21. They then compared
visible, Down-like characteristics of these animals, such as face, head and
growth measurements, with those from a known mouse model of Down syndrome.
The team reports in Science on 21 October that mice with three copies of
the critical region did not look significantly different from mice with
only one or two copies of these genes1. They also did not share the characteristic
face and head shape present in the established mouse model.
Developing interactions
This demonstrates, in mice at least, that having just a few genes present
in three copies is not enough to cause key features of Down syndrome. The
researchers are confident that the finding applies to humans too, and believe
that the condition is likely to be caused by complex genetic interactions
between much larger numbers of tripled genes.
"The very simplistic explanation we had before was wrong," says Roger Reeves,
from the Johns Hopkins University School of Medicine, Baltimore, who is
one of the study's co-authors.
Reeves suggests that researchers should examine how characteristics of Down
syndrome develop, as well as studying the genetic make-up of those with
the condition.
"You can't look at any of this in isolation. You can't just look at one
gene at a time. We need to be looking at the whole developing system," he
says.
Such a complex system of interdependence will make it more difficult to
treat Down syndrome by targeting particular genes. But researchers should
not necessarily abandon this approach, according to David Nelson from Baylor
College of Medicine, Texas.
"This is just part of the story. There may be a small number of genes responsible
for other aspects of Down syndrome, such as heart defects. So I don't think
it completely rules out that line of thinking," Nelson says.
References
Olson L. E., Richtsmeier J. T., Leszl J & Reeves R. H. Science, 306. 687 - 690 (2004).