Transcript Family History and the Pedigree

Human Pedigree and
Genetic Disease
Gregor Mendel
Thomas Bayes
Common Pedigree Symbols
Male
Marriage
Female
Sex
Unknown
Consanguineous
Marriage
Affected Female
No Known
Pregnancy
Female Carrier of
Sex-linked Recessive
Female Carrier
(Heterozygous)
Dead
Unmarried
Divorce and
Remarried
Common Pedigree Symbols
Pregnancy in
Progress
3
Three Males
5
Five Individuals
(both sexes)
Dizygotic
(nonidentical,
fraternal) twins
Monozygotic
(identical) twins
Spontaneous
Abortion
Proband, propositus,
or index case
Adopted Child
Happy new wife!
Famous Kid
Bad Divorce
Triplets!
Mistakes in Meiosis

Chromosomes fail to separate properly during
meiosis, i.e., nondisjunction

ANEUPLOIDY -- an abnormal number of
chromosomes

Examples:
– Down’s Syndrome (Trisomy-21)
– Klinefelter’s Syndrome
– Turner’s Syndrome
Polygenic Inheritance

Most human characteristics are polygenic,
meaning they are influenced by several
genes, e.g. skin color influenced by 3-6
genes; also, eye color, height, hair color
 Complex characters are those that are
influenced strongly by both the
environment and genes, e.g., diabetes,
heart disease, stroke, skin color, height
More patterns of inheritance…..





Multiple alleles - genes with three or more alleles, e.g.,
ABO blood groups
Incomplete dominance – condition that results in a
display of a trait that is intermediate between the two
parents
X-linked traits – determined by x-linked genes, e.g., color
blindness
Sex-influenced traits – usually autosomal, e.g. baldness
is influenced by testosterone
Single-allele traits – more than 200 human traits are
governed by single dominant alleles, e.g., Huntington’s
disease
Detecting Genetic Disease

Genetic Screening – examination of a person’s genetic
makeup involving karyotypes, blood tests for certain
proteins, or direct tests of DNA
– 200 genetic disorders can be detected in the fetus
– Amniocentesis – removal of amniotic fluid from the sac
that surrounds the fetus between the 14th and 16th week of
pregnancy
– Chorionic villi sampling – sample of cells derived between
the 8th and 10th week from the zygote - cells grow
between the mother’s uterus and the placenta; cells
chromosomes, and proteins analyzed
Detecting Genetic Disease
– Chorionic villi sampling – CVS can help identify
chromosomal problems such as Down syndrome
or other genetic diseases such as cystic fibrosis,
Tay-Sachs disease and sickle cell anemia. CVS is
considered to be 98% accurate in the diagnosis of
chromosomal defects, such as Down syndrome.
Normal Female Karyotype
Normal Male Karyotype
Down’s Syndrome

Smallest chromosomes with 1500 genes affected.
 Occurs in 1 out of every 800 babies.
– 40% congenital heart defects.
 Can result from maternal age or chromosome
defect.
Klinefelter’s Syndrome

Occurs in one out of every 1000 males.
 Results from extra X chromosome = XXY.
 Males tall, sterile, small testicles, and mentally
handicapped.
Turner’s Syndrome

Occurs in females.
 Results from XO condition.

Female is short, sterile, and mentally impaired.
Single Gene Inheritance
Pedigree Analysis

Autosomal dominant traits
– Huntington’s Disease on chromosome #4
– Marfan Syndrome on chromosome #15
– Breast Cancer on chromosomes #17
 Autosomal recessive traits
– Tay-Sachs Disease on chromosome #15
– Cystic Fibrosis on chromosome #7
– Sickle Cell Anemia on chromosome #11
 X-Linked Disease (Sex-Linked)
– Hemophilia
--Duchenne’s muscular dystrophy
– Color Blindness
Autosomal Dominant Traits

Present on any autosomal chromosome,
i.e., 1-22.

One allele present = disease present, i.e.,
a person has it or he or she does not
Huntington’s Disease

Begins to show up by age 45-55, within 1020 years, death is eminent.

Progressive degeneration of nervous system;
irregular body movements and slurred speech.

If one parent has HD, offspring have 50%
chance of inheriting disease.

Autosomal dominant on chromosome 4; 1
in 10,000 births
Huntington’s Disease
Hh
hh
What are the genotypes of the parents?
Marfan Syndrome

Symptoms: long limbs, loose joints,
deformed vertebral column, crowded
teeth, rupture of large arteries
 1 in 20,000 Americans born with it
 Caused by lack of fibrillin-1, a major
component of connective tissue found in
ligaments and blood-vessel sheaths
Autosomal Recessive

Disease manifests itself if offspring inherits
one recessive gene from each parent.
 If parents are carriers, 25% of offspring
will have disease.
Tay-Sachs Disease




1 in 600 Jews of European descent born with it
Lipids deposited in nervous system, causing brain to be
damaged -- blindness, loss of movement, mental
deterioration.
No break down of cellular wastes in lysosome due to
absence of hexosaminidase A – mutation causes nerve
death
Symptoms appear around 6 months of age and victims die
due to paralysis and/or convulsions before the age of five.
Tay-Sachs Disease
Tt
Tt or TT
Tt
tt
Tt or TT TT or Tt
What are the genotypes of all TT or Tt
individuals in this family?
Tt
Tt
tt
Cystic Fibrosis

Found in Caucasians.
– Most common lethal genetic disorder among white
Americans.
– Autosomal recessive on chromosome 7

Thick mucus produced in lungs, intestines,
and pancreas.

1/20 of Caucasian population are carriers.
– One in 2,000 children born to white Americans
inherits the disorder.
– CF kills ~500 children and young adults each year.
Sickle Cell Anemia





Found in both African Americans and Hispanics of
Carribbean ancestry (1 in 500 African Americans)
Hemoglobin (oxygen-carrying protein)
differs by ONE amino acid.
Sickling of cells occurs, clogging vessels -- stroke.
In U.S., 60,000 people have it; 30 million carriers.
Autosomal recessive on chromosome 11
X-Linked Disorders

Found on the 23rd pair of chromosomes,
i.e., the sex chromosomes.

Usually shows up in males due to Y
chromosome lacking genes, i.e., one
recessive gene in males produces disorder.

Mother carriers pass gene to sons.
Hemophilia -“Bleeder’s Disease”




Deficient blood coagulation due to absence of
coagulation factor 8 that helps cause blood to
clot.
50% of daughters will also be carriers.
1 in 7,000 born with it
X-linked recessive on chromosome X
XHXh
XHY
Duchenne’s Muscular
Dystrophy

Progressive destruction of muscles.

Patients wheelchair bound by teens.

Female carriers can be detected by
presence of creatine kinase.

Can be detected by the 20th week of
gestation.
Duchenne’s Muscular
Dystrophy
XDXd
XDY
Color Blindness
Red-Green Color Blindness
Multiple Alleles

Blood type, using I gene.
 Human blood types include:
Phenotype
Genotype
–A
IAIA or IAi
–B
IBIB or IBi
–AB
IAIB (Universal Recipient)
–O
ii (Universal Donor)
If a child has type O blood and its mother has type A,
could a type B man be the father? Why couldn’t a blood
test be used to prove he is the father?