Download 5. Complex Pedigrees

Biology 311 Human Genetics
Lecture 5 Complex Pedigrees
Fall 2006
Reading: Chap. 4 pp. 106-116
Lecture Outline:
1. Common traits
2. Penetrance
3. Variable expression
4. New mutations
5. Quantitative traits
Lecture:
1. Common traits


Recessive traits that occur frequently in population can give appearance of
dominance.
Individuals with trait commonly marry into pedigree.
Example: Blood group O in pedigree Fig. 4.5A
ABO blood groups
A is dominant to O
AA and AO = A blood type
OO = O blood type
Type O blood is common in population
2. Penetrance: probability that a person who has genotype will show the character.
But dominant traits show different degrees of penetrance. Can have trait but not show it
due to
 Different genetic makeup for other loci
 Different environment, lifestyle
 Chance
Many traits are multifactorial; show incomplete penetrance and involve many genes.
Fig. 4.6
Late onset diseases: i. e. Huntington's
 Age-related penetrance due to unknown factors
 Slow accumulation of toxins
 Slow tissue death
 Lack of repair
1
3. Variable expression: Different levels of a gene product are made despite similar
number of copies of gene.
Due to:
 Environmental signals that regulate genes
 Different genetic make-up
 Chance
Anticipation: tendency of some variable dominant conditions to become more
severe in successive generations.
Found to be a molecular basis for this effect for some diseases associated with unstable
expanding triplet trinucleotide repeats:
 Fragile X syndrome
 Myotonic dystrophy
 Huntington disease
4. New mutations are source of much genetic disease
 natural selection acts on individuals who have dominant traits that reduce viability
or reproduction or on males with X-linked recessive traits.
Difficult to assess normal couple with no relevant family history who have a child with
severe abnormalities.
Duchenne muscular dystrophy can be new mutation.
Example of pedigree with new mutation: Figure 4.8
X-linked recessive trait in family with no history of DMD
To determine this
 DNA testing of proband, mother, father, grandparents
 Only proband shows DMD allele, therefore new mutation
5. Quantitative traits
Continuously variable traits
first studied by Francis Galton
i.e. height, weight
vs. Mendelian traits, which are dichotomous characters +/R. A. Fischer demonstrated that characters controlled by many independent Mendelian
factors would display quantitative variation.
Variable character depending on many genes will show a normal distribution (Fig. 4.11)
Example for I.Q. that was determined entirely by genes.
2
Normal distribution is specified by
 Mean
 Variance or standard deviation (square root of the variance)
Variances are additive
 Can be broken down into environmental and genetic variance
Heritability = proportion of variance that is genetic.
Threshold model for polygenic (=many traits involved) traits, Fig. 4.14.
Conditions that run in a family due to many genes interacting with the environment—
may see a threshold effect of increased liability.
3