Exploring Chromosome 7
The search for chromosome regions linked to autism has indicated
that there are genes associated with autistic disorder on chromosome 7. The candidate
genes on chromosome 7 include: FOXP2, WNT2, RELN, HOXA1, and HOXB1.
The RELN gene
The RELN gene on chromosome 7 is thought to help regulate how brain cells form and organize the brain
during fetal development. The RELN gene has a polymorphic trinucleotide repeat, which is a portion of
a gene that repeats over and over a variable number of times (the segment that repeats is called "a
repeat"); the number of times it repeats varies in different people. Researchers at Duke University
examined the repeat in RELN in Collaborative Autistic disorder Team study participants and Autism
Genetic Resource Exchange (AGRE) families, and found no significant evidence for an association between
the number of repeats in the RELN gene and autistic disorder. However, when they looked only at the
AGRE families, they did see evidence of a possible association between RELN genes with 8-10 repeats
and autistic disorder.
In 2001, Dr. Persico and his colleagues reported that some individuals with Autistic disorder
had 10 or more repeats in the RELN gene. While the differences in these research findings may seem
confusing, together they suggest that variations in the RELN gene warrant further study.
The FOXP2 gene
The first gene associated with a speech and language disorder has recently been identified. The
FOXP2 gene, reported by Lai and colleagues in 2001, is associated with a rare disorder in which
people have developmental verbal dyspraxia (difficulty with facial movements necessary for
articulation) and problems with language processing and grammatical skills. Since people with
autistic disorder also have problems with speech and language development, this gene was initially
considered to be a candidate gene for autistic disorder. However, preliminary reports indicate that
this gene is not associated with autistic disorder.
References
- Lai CS. Fisher SE. Hurst JA. Vargha-Khadem F. Monaco AP. A forkhead-domain
gene is mutated in a severe speech and language disorder. Nature. 413:519-23,
2001 Oct 4.
- Wassink, TH, Piven, J, Vieland, VJ, Pietila, J, Goedken, RJ, Folstein, SE,
& Sheffield, VC. (2002). Evaluation of FOXP2 as an autism susceptibility gene.
American Journal of Medical Genetics (Neuropsychiatric Genetics), 114:566-569.
- Newbury, DF, Bonora, E, Lamb, JA, Fisher, SE, Lai, CS, Baird, G et al.
(2002). FOXP2 is not a major susceptibility gene for autism or specific language
impairment. American Journal of Human Genetics, 70:1318-1327.
The WNT2 gene
The WNT2 gene on the long arm of chromosome 7 is involved in directing the fate of cells —
where they go and what they do in the body. There are several types of WNT genes, and many are
active in both the developing nervous system of fetuses and the mature nervous system of adults.
In 2001, Wassink and colleagues reported finding a variation in the WNT 2 gene more often than
expected in individuals with autistic disorder, especially in a subset of people with autistic
disorder and severe language delays. Additional researchers will need to investigate this gene
in other families to fully understand whether the WNT2 gene is related to autistic disorder.
The HOXA1 and HOXB1 genes
The HOXA1 and HOXB1 genes, on a different part of chromosome 7, are involved in the development of a part
of the brain called the hindbrain. The HOX genes are candidate genes for autistic disorder because some
individuals with autistic disorder have changes in the hindbrain. Rodier and her colleagues found certain
variations in these genes in individuals with autistic disorder. They found that variations in the HOXA1
gene occurred at different frequencies in people with autistic disorder than would be statistically expected.
However, because they also found variations in these genes in individuals without autistic disorder, whether
the HOXA1 and HOXB1 genes are directly involved in autism in not yet clear.
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