Pedigrees & Genetic Analysis

Learning Objectives By the end of this class you should understand: The purpose of a pedigree How to read and interpret a pedigree chart How to construct a pedigree chart given sufficient information How to use a pedigree chart to identify the behavior of a particular allele How to construct a Punnett square for a particular pedigree chart crossing The nature of autosomal vs. sex-linked genes

Patterns of Inheritance Autosomal chromosomes Autosomal dominant Autosomal recessive Sex-linked X-linked Y-linked Mitochondrial

Pedigree Chart A pedigree chart, or just pedigree, shows family history for a particular condition Can be for hair color, eye color, etc Most commonly for a genetic disorder Can be used to determine the nature of the inheritance

Pedigree Symbols A key is typically provided If it is not, these are the standards: Male is square, female is circle Age left-right Marriage is horizontal line Offspring is vertical branched line

Single-gene Tracking Tracking a genetic disorder typically involves monohybrid crosses only More dihybrid cross practice later Typically disorders are at two-allele loci Multi-allele locus is like blood type & hair color Each cross can also be represented by a Punnett Square We will practice this!

Proband The first person to be identified as having a genetic disorder is called the proband The proband may be the first person to receive treatment or be diagnosed Alternatively, sometimes the progenitor ancestor is identified as the proband

Autosomal Dominant Disorder Does not “skip” any generations Approximately 50% of the offspring of every affected individual is also affected Punnett Squares typically heterozygote crossed with recessive homozygote

Autosomal Dominant

Autosomal Recessive Disorder Often “skips” generations When both parents are carriers, about 1 in 4 offspring are affected When one parent has the condition: 1 in 2 offspring are affected and other half are carriers OR all are carriers

Autosomal Recessive

SPECIAL NOTE: An autosomal recessive may resemble an autosomal dominant if the allele is very common Essentially most crosses become aa x Aa which is hard to distinguish from Aa x aa Look for unaffected offspring of two affected parents Indicates dominant Look for affected offspring of two unaffected parents Indicates recessive

Example of Ambiguity

Dominant or Recessive?

Sex-linked Traits X-linked Can be dominant or recessive Y-linked Passed from father to son Mitochondrial Passed from mother to all children

Y-Linked Inheritance The Y chromosome causes a fetus to become male Any gene on the Y chromosome will only be passed on to male children Exception: CAIS, an XY individual who is female

Y-Linked Inheritance

Mitochondrial Inheritance All of a human's mitochondria are passed down from the mother Sperm mitochondria are not absorbed into the fertilized egg All offspring of an affected female have the disorder, but not an affected male

Mitochondrial Inheritance

X-Linked Traits X-linked traits are coded for by genes on the X chromosome Women have two X chromosomes and men have one This means expression patterns are different in men and women!

X-Linked Dominant X-Linked Dominant will affect men and women differently All of an affected man's daughters will express the disorder None of an affected man's sons will express the disorder Half an affected woman's offspring will express the disorder

X-Linked Dominant

X-Linked Recessive Several disorders are X- linked recessive Colorblindness, hemophilia For a woman, both X chromosomes must be defective Men only have one X so if it is defective they express the disorder

X-Linked Recessive

Patterns of Inheritance Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Y-linked Mitochondrial

Dihybrid Cross One practical use for a dihybrid cross is to consider gender as a factor in an autosomal cross Particularly if there is a sex-linked trait as well Strategy: determine what the gametes are first AaXX' x AaXY AX AX' aX aX' AX AY aX aY AXAX'aXaX' AXAAXXAAXX'AaXXAaXX' AYAAXYAAX'YAaXYAaX'Y aXAaXXAaXX'aaXXaaX'Y aYAaXYAaX'YaaXYaaX'Y

Dihybrid Practice: Heterozygous Aa x Aa cross between a colorblind man and a noncarrier woman What are the possible outcomes? If the autosomal gene is a recessive disorder what is the probability of a child having the disorder? What is the probability of a boy having each disorder? A girl? What is the probability of a child having both?

Partner Practice (time permitting) Everyone choose one of the five patterns and draw your own pedigree chart! Be sure it has at least 3 generations and thhere should be at least five crosses of interest Trade with a partner and analyze which pattern(s) it matches!

Have a good weekend!