2/12/16
BIOLOGY 207 - Dr.Locke
Lecture#17 - Pedigree Analysis
Required readings and problems:
Reading: Open Genetics, Chapter 5
Problems: Chapter 5
Optional
Griffiths (2008) 9th Ed. Readings: pp 66-76
Problems: 9th Ed. Ch. 2: 29, 37-45, 50-51, 54, 59-61, 64-66
Campbell (2008) 8th Ed. Readings: Concept 14.4
Concepts:
How do we analyze inheritance patterns in humans?
1. Mendel's experimental methods cannot be applied to humans.
2. Human genetic disease can only really be identified by family studies.
3. Most kinds of hereditary patterns are evident in humans pedigrees.
Biol207 Dr. Locke section
Lecture#17
Fall'11
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Mendel's experimental Methods
1. Controlled genetic crosses -> make (force) a cross of known parentage
2. Well characterized, inbred, true breeding strains
3. Follow crosses over several generations
4. Create many progeny -> accurate and complete representation of the results of a
cross (e.g. parentals vs. recombinants)
These techniques are powerful and are used today.
But they are not practical for examining human heredity, e.g. inherited genetic diseases.
They can not be applied to humans
1. No controlled crosses -> ethical considerations
2. No true breeding or inbred strains
3. Difficult to follow crosses for more than about 2-3 generations
4. Few progeny can be obtained (relatively speaking)
We need to examine heredity in humans because:
1. Genetic diseases. e.g. CF, Sickle-cell anemia, Huntington's, Cancer (various
types), [Downs/Turners/Klinefelters syndromes].
2. Parent-offspring testing (Paternity-testing)
3. Forensic analysis - O.J. Simpson Trial (USA), Guy Moran (Canada).
4. Risk groups --> future tests for all types of diseases
(you'd be surprised what will be possible).
Biol207 Dr. Locke section
Lecture#17
Fall'11
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Hereditary diseases
1) An important aspect of medical practice.
2) Physicians can't use Mendelian crosses to diagnose the genetic
diseases of their patients.
3) Physicians (human geneticists) resort to constructing a family
history or Pedigree
(matings, parents and progeny of family members).
4) Search through these matings to find informative crosses (those
that resemble Mendelian crosses) that have occurred by
chance.
5) A history of matings is shown in diagrammatic form.
There is a conventional set of symbols.
Male, female, mating, generation, affected individuals, propositus
(proband) consanguineous marriage (between closely related
individuals), to construct the pedigree -> analysis of the inheritance patterns.
We use the principles of Mendelian inheritance to understand the patterns in the
pedigree.
Note: Without the basic science research on the mechanisms of heredity (by
Mendel and others, on non-human organisms) an understanding of the mechanisms of
human (and other useful organisms - eg. crops, livestock) would have been very much
more difficult. -> Basic Research Makes Sense!
Biol207 Dr. Locke section
Lecture#17
Fall'11
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Patterns of inheritance in Pedigrees
We will use humans as an example here, but this applies to all other organism with
X/Y sex chromosomes and autosomes.
Y-linked Traits (genes):
1 - gene on Y chromosome
2 - only males affected (remember only females in ZW system)
3 - affected male transmits to all sons
4 - affected male does not transmit to daughters
e.g. hairy ear rim
Fig 2-40 (Griffiths 9th Ed.)
Biol207 Dr. Locke section
Lecture#17
Fall'11
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X-linked Dominant Inheritance
Characteristics:
1) Dominant --> observed in each generation
2) Female heterozygote transmit their trait to 1/2 their children of either sex
3) Male affected transmit to all his daughters and no sons
4) Affected females are more common than affected males
5) No transmission from father to son
e.g. hypophosphatemia - a type of vitamin-D resistant rickets
Biol207 Dr. Locke section
Lecture#17
Fall'11
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X-linked recessive Inheritance
Characteristics:
1) Affected males are more common than affected females
2) No transmission from father to son
3) Daughters of affected males are carriers (heterozygotes)
4) Trait is transmitted from heterozygous carrier female to 1/2 sons
5) Affected females have affected fathers and carrier mothers
e.g. hemophila, red-green colour blindness
Biol207 Dr. Locke section
Lecture#17
Fall'11
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Autosomal Dominant Inheritance
Characteristics:
1) Dominant - must be observed in each generation
2) Affected individuals (males and females) transmit to 1/2 children, sons and
daughters
3) Males and females equally likely to have the trait
e.g. - pseudo-achondroplasia (dwarfism)
Biol207 Dr. Locke section
Lecture#17
Fall'11
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Autosomal-recessive inheritance
Characteristics
1) Trait may skip generations
2) Affected offspring generally have normal (but heterozygous) parents
3) Males and females equally affected
e.g. - PKU (phenylketonuria)
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Lecture#17
Fall'11
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The pedigree analysis above is simple.
It assumes:
1.- Single gene locus
- often true, but not always
- some traits involve 2 or more loci
2.- Simple dominance and recessive alleles
- not always true; remember incomplete dominant alleles, etc. are also possible
(white-pink-red flowers of the 4 o'clock plant)
3.- Complete penetrance
- phenotype accurately reflects the genotype
- e.g. recessive alleles always shows the trait in recessive homozygotes or
dominant alleles always show the trait in heterozygotes
Note: As we learn more about patterns of inheritance the interpretation of pedigrees
becomes more complex
- many genes are often involved
- gene expression is not simple
- inheritance is also not simple
Biol207 Dr. Locke section
Lecture#17
Fall'11
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