923
CHAPTER TWENTY-FOUR
Genetics and Genomics
illness with tragic clarity—his grandmother had
recently died after a F
fteen-year battle with the
disease, his father lived in a nursing home where
his uncontrollable movements could be con-
trolled, and his older brother Mike was just start-
ing to show symptoms. Inherited in an autosomal
dominant manner, HD strikes every generation
and a±
ects males and females. If Stuart had the
mutation—a “triplet repeat” in which a sequence
of DNA, CAG, is present in many extra copies—
he, too, would develop the behavioral and cogni-
tive changes and motor symptoms of HD. He was
about to get married and would use the informa-
tion in his decision about having children.
X-Linked Recessive Inheritance:
Duchenne Muscular Dystrophy
Malcolm had always been a clumsy child, but
when he started tripping more often at the age of
4, his mother Emelda took him to a pediatrician.
The doctor observed Malcolm walking, noticing
his enlarged calf muscles, and also had the boy
rise from a seated position. Rather than standing
directly, he pushed o±
with his hands. He’d been
standing that way for so long that Emelda had
thought it normal. The doctor thought otherwise
and referred the entire family to a muscular dys-
trophy clinic at a nearby medical center.
Genetic testing revealed that the gene
that encodes a protein called dystrophin was
absent—Malcolm had Duchenne muscu-
lar dystrophy. His muscle cells lack a protein
required to withstand the force of contraction.
His skeletal muscles were already affected,
and he would be in a wheelchair by age ten.
Then his cardiac and smooth muscle cells
might be a±
ected too.
The family met with a genetic counselor.
She asked questions about Malcolm’s cousins
on his mother’s side, but they were all girls. The
counselor explained that Duchenne muscular
dystrophy is caused by a mutation in a gene on
the X chromosome. It passes from carrier moth-
ers, such as Emelda, to a±
ected sons. Malcolm’s
father George could not have transmitted the
gene, because he passed his Y chromosome to
his son, not his X. The counselor told Emelda and
George that they could have their younger son
Thad tested. He, too, tripped often, but the par-
ents had attributed his clumsiness to imitating his
brother. Thad did not have the mutation.
24.1
CLINICAL APPLICATION
Genetic Counselors Communicate Modes of Inheritance
Reasons to seek genetic counseling:
Family history of abnormal chromosomes
Elevated risk of single gene disorder
Family history of multifactorial disorder
Family history of cancer
Genetic counseling sessions:
Family history
Pedigree construction
Information provided on specific
disorders, modes of inheritance,
tests to identify at-risk family
members
Testing arranged, discussion of
results
Links to support groups, appro-
priate services
Follow-up contact
FIGURE 24A
The genetic counseling process.
G
enetic counselors are medical profes-
sionals who help families understand the
implications of an inherited illness and
guide them in obtaining tests, treatments, and
services (F
g. 24A). The tools of the genetic coun-
selor include pedigree charts, family and medical
histories, communication skills, and compassion.
²or disorders caused by a single gene, the coun-
selor must explain the mode of inheritance—as
the following real cases demonstrate.
Autosomal Recessive Inheritance:
Cystic Fibrosis
Molly and Russell received unexpected news dur-
ing her fourth month of pregnancy—a routine
blood test had revealed that she was a carrier of
C². She had one wild type copy of the gene and
one mutant copy. That allele was rare and asso-
ciated with mild disease, the genetic counselor
explained. Did Molly or any of her blood rela-
tives have frequent respiratory problems? Molly
thought a moment. Her mother and maternal
grandmother seemed to have bronchitis nearly
every winter, and just last year her mother had
been hospitalized with pneumonia. One of her
brothers had frequent colds, and she herself had
always su±
ered from sinusitis.
Molly’s family history was consistent with C².
The next step to better determine risk to the fetus
was to have Russell tested. If he was a carrier, too,
then the fetus faced a one in four chance of hav-
ing inherited C². The severity would depend upon
which allele Russell had. Russell was homozygous
for the wild type allele. Had he carried a mutation
too, further testing could have diagnosed the
fetus. C² testing is routine for pregnant women
and newborns are screened for the disease.
Autosomal Dominant Inheritance:
Huntington Disease
Stuart had completed several sessions with his
genetic counselor and felt he was ready to take
the predictive test for Huntington Disease (HD). It
hadn’t been an easy decision. At age thirty, he was
able to see the inheritance pattern of his family’s
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