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allied
academies
International Conference on
FAMILY MEDICINE AND FAMILY PHYSICIANS
October 16-17, 2017 | Toronto, Canada
Arch Gen Intern Med 2017 | Volume 1 Issue 3
H
untington’s disease (HD) is an autosomal dominant,
progressive neurodegenerative disorder which bears
excessive repetition of CAG tri-nucleotides in the
HTT
gene.
When the number of such repetitions reaches a certain level,
the protein encoded by this gene, huntingtin (htt), undergoes
a structural change as a result of the increased number of
glutamine residues. Numerous studies have investigated
the origin of the disease by correlating haplotypes of the
HTT
region to ethnicity. Many SNPs are highly sensitive
markers of disease chromosomes and have stronger linkage
associations with expanded CAG. These disease-associated
SNPs constitute a cluster of similar haplotypes: haplotype A
was found in a vast majority of affected chromosomes. The
majority of HD chromosomes in Europe contain haplotype A
and East Asian populations (China and Japan) haplotype C.
The aim of this study was to investigate the genetic diversity
of the
HTT
gene expanded alleles (>35 CAG), intermediate
alleles (27–35 CAG), and control alleles (<27 CAG) in
Brazilian patients and unaffected individuals. Affected and
unaffected samples from 33 Brazilian HD pedigrees were
tested for genetic markers associated with the A1
HTT
haplotype (European and Amerindian A1 SNPs), following
the methodology suggested by Kay et al., 2015. Concerning
the HD chromosomes, 52% of HD families were classified in
haplo-group A1. In contrast, haplo-group A1 accounted for
only 5% of chromosomes of the Brazilian general population
(<27 CAG). Haplo-group C was present in approximately
22% of the normal chromosomes but only in 6% of the HD
chromosomes. The HD chromosomes had an average size
of 44 (39 to 62) CAG repeats, and the normal chromosomes
had 17 (14 to 30). The families included in the A1 haplo-
group were also tested for the presence of a specific SNP
which distinguished A1 Amerindian from A1 European. Only
three HD families belonged to A1 Amerindian haplo-group,
whereas the others to the A1 European. CAG expansion
in European populations does not occur randomly, but is
associated with specific
HTT
haplotypes (A1 and A2). There
is no treatment for HD except palliative therapy; therefore
silencing the HD mutant allele is an attractive strategy for
future intervention because it would target the cause of HD.
HD allele-specific silencing is important in order to preserve
wild-type
HTT
function. Haplotype searching can play an
important role in order to identify Brazilian patients who
could benefit the allele-specific silencing in the future.
e:
polucita@yahoo.com.brHuntington disease (an unpublished epidemiological study)
Luciana de Andrade Agostinho
Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Brazil