Download 4. Pedigree Analysis

Biology 311 Human Genetics
Lecture 4 "Pedigree Analysis"
Fall 2004
Reading: Chap. 4 pp. 102-106
Lecture Outline:
1. Mendelian genetics
2. Pedigree symbols (review)
3. Pedigree patterns
4. Mitochondrial inheritance
Lecture:
1. Mendelian genetics


simplest genetic characters=Mendelian traits
one genetic locus mainly determines characteristic
Mendel deduced:
 Genes are inherited as discrete units
 Two versions (alleles) of a gene determine each trait
Terms to know:
Dominance
Recessiveness
Homozygous
Heterozygous
Hemizygous
Genotype
Phenotype
Be able to carry out monohybrid and dihybrid crosses.
2. Pedigree Symbols
See Fig. 4.1
Male
Female
Sex unknown
Affected
1
Unaffected
Carrier
Marriage or mating
Consanguineous marriage
Twins
Dead
Generations I, II, etc.
Individuals 1, 2, 3, etc.
Proband or propsitus
3. Basic Pedigree Patterns
a.
b.
c.
d.
e.
Box 4.1 and Fig. 4.2
autosomal dominant inheritance
autosomal recessive inheritance
X-linked recessive inheritance
X-linked dominant inheritance
Y-linked inheritance
a. Autosomal dominant
A=dominant
a=recessive
Usually involves matings of an affected individual with an unaffected individual.
Aa x aa
1/2 Aa dominant trait
1/2 aa recessive trait
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Examples:
Familial hypercholesterolemia
Hereditary colon cancer
Huntington disease
Neurofibromatosis
Achondroplasia (dwarfism)
b. autosomal recessive
A=dominant trait (normal)
a=recessive trait (unaffected)
matings are usually between two unaffected individuals
transmission of the trait occurs when two heterozygotes mate
Aa x Aa
1/4 AA
2/4 Aa
1/4 aa
3/4 A- normal
1/4 aa recessive trait
Examples:
Tay-Sachs
Cystic fibrosis
Sickle cell anemia
Phenylketonuria
c. X-linked recessive trait
Xa=recessive trait
XA=normal dominant trait
X-linked recessive trait affects mainly males
Usually is passed from a carrier mother to her son
XaXA
x
XAY
1/4 XAXa
1/4 XAXA
1/4 XAY
1/4XaY
female carrier (normal)
female normal
male normal
male affected
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Examples:
Hemophilia A
Duchenne muscular dystrophy
Red-green color blindness
d. X-linked dominant inheritance
XA=dominant trait (affected)
Xa=recessive trait (normal)
Affects males and females, but occurs more often in females
Usually an affected individual marries an unaffected individual
XAXa
x
XaY
1/4 XAXa
1/4 XaXa
1/4 XAY
1/4 XaY
affected female
normal female
affected male
normal male
Example:
Vitamin D-resistant rickets
e. Y-linked inheritance
affects only males
affected males have an affected father
very few Y-linked traits; maleness only known Y-linked character
XX
x
XY*
XX
XY*
normal female
affected male
No Y-linked diseases known
4. Mitochondrial Inheritance



Mendel's laws apply to nuclear genes, not mitochondrial genes.
A few genes are carried in the small circular DNA of mitochondria.
Defects in mtDNA are responsible for some human diseases.
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
These diseases are maternally inherited because at fertilization only
female parent (egg) contributes mitochondria to zygote, portion of sperm
containing the mitochondrion does not enter egg.
Example:
MtDNA associated deafness shown in Fig. 4.4
5. Complementation


Box 4.2
In complementation, mutant characters are combined and the result is
restoration of the wild type phenotype.
Use to determine whether two recessive characters are due to alleles at
the same gene or to two different genes.
Example: autosomal deafness due to two distinct genes. Fig. 4.3
Pedigree shows that offspring of two parents affected by two different types of
deafness are unaffected.
Locus heterogeneity: Where the same clinical phenotype can result from
mutations from any of several different genes.
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