Lecture 13 ~ 14            Genetics Of Human Disease

I. Recessive Genetic Disorder

A.  Autosomal

1.Phenylketonuria (PKU)

Recessive inherited disorder on autosome, 1/10,000 births in U.S.
Disorder syndrome:
Can not break down phenylalanine.  The accumulated Phe is toxic, and can cause mental retardation.  If the deficiency is detected in the newborn, retardation can usually be prevented with a strict diet, low in Phe, that allows normal development.

2. Cystic fibrosis

Strikes 1/2500 whites of European descent, much rarer in other groups.  1/25 whites (4%) is a carrier. Recessive inherited disorder on autosome.

Disorder syndrome:
Abnormally high concentration of extracellular chloride, which causes the mucus build up in the pancreas, lungs, digestive tract and other organs, a condition favors bacterial infection.  Children die before the age of five.

3. Sickle-cell anemia:
Recessive inherited disorder on autosome.  It strikes 1/400 African-Americans.  1/10  African-Americans has sickle-cell trait (Devaughn Darling, freshman linebacker of FSU).

Disorder syndrome:

Caused by the substitution of a single amino acid in the hemoglobin protein of red blood cells, the abnormal hemoglobin crystallizes when oxygen content of blood is low, causing RBC to become sickle shaped.

4.  Tay-Sachs disease:
Recessive inherited disorder on autosome at the organismal level.  The normal allele and the Tay- Sachs allele are codominant at the molecular level.

Disorder syndrome:

The brain cells of a baby with this disorder are unable to metabolize gangliosides, a type of lipid, because a crucial enzyme doesn’t work properly.  The accumulation of this lipid in the brain can cause brain cells gradually cease to function normally, leading to death.

B.  Sex chromosome – linked Genetic Disorder

1. Hemophilia

Sex-linked recessive trait (X-chromosome), absence of a certain protein, required for blood clotting.

2. Lesch-Nyhan Syndrome

Sex-linked recessive disease (X-chromosome), characterized by mental retardation and a tendency for self-mutilation.

II. Dominant Disorders, by a dominant autosomal gene.

A. Huntington’s Disease

A degenerative disease of the nervous system is caused by a lethal dominant allele that has no obvious phenotypic effect until 35 ~ 45 years old.

Any child born to a parent who has the allele for Huntington’s disease has at least a 50% chance of inheriting the allele and the disorder.

B. Neurofibromatosis

A genetic disease, caused by a dominant autosomal gene, that has a variety of phenotypic effects, including tumors, abnormal bone growth, enlarged head, and misshapen hands.

III. Chromosomal Disorders

A.  Chromosome structural alteration:

“cri-du-chat”  syndrome, deletion in chromosome 5.

B.  Chromosome number alteration:

Down’s syndrome, 1/700 children in US.  An extra chromosome on chromosome 21, which makes chromosome 21 a trisomy.  Each body cell has a total of 47 chromosomes.
Facial structures, short stature, heart defects, and mental retardation.

The frequency of Down syndrome correlates with the age of the mother.

Mother’s age  Down syndrome frequency
in newborns
< 29        1/3000

30 ~ 34   1/600

35 ~ 39   1/280

40 ~ 44   1/70
45 ~ 49   1/40

V. Genetic Counseling

A. Objectives

B. Tools and Tests.

1. Genetic screening

a) Carrier detection
b) Newborn testing
c) Fetal monitoring

C.  Ethical Considerations.