Pedigree Analysis

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Why perform a pedigree analysis?

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1) to determine if a trait is inherited or if it is environmentally determined
2) to explain the mode of inheritance - dominant vs recessive, autosomal vs recessive
3) to predict the risk of a trait being passed on
4) to discover if a trait is inherited along with another know characteristic

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A record of genealogy

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A pedigree

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Males in a pedigree

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squares

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Females in a pedigree

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circles

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Affected individuals in a pedigree

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shaded in

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Problems with constructing Pedigrees:

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1) written records
2) knowledge of distant relatives is likely to be incomplete
3) living relatives may be scattered making verification difficult
4) information may not be accurate do to hazy/exaggeration/
understatement
5) the phenotypic expression of the trait may vary

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Why does phenotypic expression vary?

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1) mutant allele
2) the genetic background
3) the environmental conditions

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Categories of human traits

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Autosomal Dominant
Autosomal Recessive
X-Linked Dominant
X-Linked Recessive
Y-Linked
Mitochondrial

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Autosomal Dominant Principles

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1) all affected individuals have 1+ affected parent
2) males and females are effected equally
3) males and females pass on the trait
4) most affected individuals are heterozygous
5) two affected individuals may have a unaffected child
6) the trait wont appear in the descendants of two unaffected individuals
7) the trait may be more severe or fatal in the homozygous state

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Diseases with Autosomal Dominance

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Marfan Syndrome
FH (Familial Hypercholesterolemia)

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Marfan Syndrome

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Cause - defect in 'fibrillin' a connective tissue protein
Result - tallness, weak joints

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FH (Familial Hypercholesterolemia)

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Cause - defect in the LDL receptor
norm - 130-190 affected - double that
Result - excess cholesterol sticks to the blood vessels and can cut of the blood flow, heart attack
FH can be fatal

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Autosomal Recessive Principles

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1) the trait is expressed in both sexes and transmitted by both
2) most affected individuals are children of unaffected parents
3) an unaffected and affected individual will have all unaffected offspring
4) if both parents are affected all children will be affected
5) unaffected heterozygous individuals will yield 3/4 unaffected and 1/4 affected

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Autosomal Recessive Diseases

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Cystic Fibrosis
Sickle Cell Anemia

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Cystic Fibrosis

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Cause - defect in the controls of salt and water transport
More common in Caucasians
Results - malnutrition and decrease of airways/decrease in oxygen

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Sickle Cell Anemia

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Cause - defect in the Hemoglobin gene
Red blood cell deforms into a sickle shape
Results - heart attack, organ malfunction

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X-Linked Dominance Principles

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1) There are no male to male transfers of the trait
2) All daughters of an affected male are affected
3) Affected females mated to unaffected males produce offspring where half the sons and daughters are affected
4) males are more severely affected than females
5) in the general population are twice as many affected females than males

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Female sex chromosomes

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XX

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Male sex chromosomes

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XY

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X-Linked Dominant Diseases

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Hypophosphatemia

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Hypophosphatemia

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A low level of phosphate/calcium in the blood
Cause - a defect in kidney transport system
Result - poor bone and teeth growth ; short statue skeletal abnormalities, pain

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X-Linked Recessive Principles

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1) phenotypic expression more common in males
2) NO father to son inheritance
3) an unaffected mother mated with an unaffected male can pass the trait to half her sons (it will not be observed in any daughters)
4) carrier females often have affected male/carrier female ancestors

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X-Linked Recessive Diseases

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Red/Green Color Blindness
Duchenne Muscular Dystrophy
Hemophilia

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Red/Green Color Blindness

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Cause - defect in color sensing mechanism of the eye
Result - cannot see a difference between red and green

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Duchenne Muscular Dystrophy

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Cause - defect in the protein dystrophin
Result - muscle decay/weakness, individuals cannot walk

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Hemophilia

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Cause - defects in proteins for clotting
Result - excessive bleeding

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Y-Linked Principles

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1) The phenotype is seen only in males and passed only to males
2) All of the sons of an affected male show the trait

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Mitochondrial Principles

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Inheritance is from mothers to all offspring

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Expressivity

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the range of phenotypes (e.g. disease severity) resulting from a given genotype

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Penetrance

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The probability that a disease phenotype will appear when a disease-related genotype is present (i.e. the percent of individuals with a gene that express it)

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Genetic Linkage

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"co-inheritance' of genes that physically reside on the same chromosome