DNA strand double helix 311.
(photo credit: Jerome Walker)
New Israeli research led by a Tel Aviv University geneticist has identified six
critical gene mutations in Israeli Jewish and Palestinian families, one of which
was found to have been involved in genetic hearing loss of 34 percent of Jews of
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The discovery, published Wednesday in BioMed Central’s
open-access journal Genome Biology, could help affected families undergo genetic
counseling to avoid such a defect in future children.
Prof. Karen Avraham
of the Sackler Medical School explained that most cases of early-onset hearing
loss are genetic in origin, but there are many different forms, almost a third
of which are associated with other clinical problems.
Thus, she said, it
can be difficult to pinpoint the exact genes responsible as mutations vary
between countries and populations.
But her team, which included doctors
and scientists both in Israel and at Bethlehem University of the Palestinian
Authority, used “targeted genomic capture and massively-parallel sequencing to
identify genes for hereditary hearing loss in Middle Eastern
They screened a total of 246 genes in 11 unrelated individuals
known to be responsible for human or mouse deafness.
All of the
individuals were believed to have hereditary deafness.
Once a mutation
was found, it was tested in an extended pool of families with hearing loss and
compared to data for people with normal hearing.
One mutation was found
in 34% of the Moroccan Jewish population but not in any other Israeli Jews,
while another was discovered in a Palestinian Arab family.
that “the two-tier method we used allowed us to scan exons of genes, thought to
be involved in hereditary deafness, and their flanking sequences. This meant
that we were able to quickly target specific genes and find multiple mutations
responsible for hearing loss.
Use of genomic analysis in early clinical
diagnosis of hearing loss will enable prediction of related phenotypes and show
us where to look to find the biological mechanisms involved in hearing
She noted that ordinary gene sequencing is expensive and
time-consuming, but exome sequencing – focusing on exons, which are short,
functionally important DNA sequences that represent regions in genes translated
into protein and the untranslated regions flanking them – is much more rapid and
cheaper to perform.
When only the individual’s exons are sequenced, by
first capturing the DNA with relevant probes, researchers can zoom in on
specific sites, reducing the amount of code they need to cover, to find
mutations that cause disease.
Avraham, of TAU Sackler Medical Faculty’s
department of human molecular genetics and biochemistry, said that her team has
“had the DNA in our freezer for 12 years, unable to find a result, but in one
month using the new technique, we were able to solve many family
“Each family that comes to a clinic cares very much why they are
deaf, and for many of them, we can provide an answer in a much more reasonable
amount of time.” She noted that the Palestinian mutation was rare, and only one
“We are discussing why we found fewer mutations in this group,
but the relevance of finding mutations is for both populations.”