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Today... Analyze pedigrees to determine the mode of inheritance of a specific trait Determine the chance of offspring having a specific trait based off pedigree analysis In humans, pedigree analysis is an important tool for studying inherited diseases figure out the genetic basis of a disease or trait from its inheritance pattern predict the risk of disease in future offspring in a family (genetic counseling)

Today... Pedigree analysis Basic patterns of inheritance autosomal, recessive autosomal, dominant X-linked, recessive X-linked, dominant (very rare) Y-Linked Mitochondrial inheritance X-rec. X-dom. Mitochondrial and Y-linked (sex-linked traits)

Autosomal recessive traits Trait is rare in pedigree Trait often skips generations (hidden in heterozygous carriers) Heterozygous parents will have about ¼ of kids affected Trait affects males and females equally Usually, affected kids have normal parents If both parents are affected—all kids will be

Autosomal recessive diseases in humans Most common ones Cystic fibrosis Sickle cell anemia Phenylketonuria (PKU) Tay-Sachs disease For each of these, overdominance (heterozygote superiority) has been suggested as a factor in maintaining the disease alleles at high frequency in some populations

Autosomal dominant pedigrees Trait is common in the pedigree Males and females equal Affected offspring must have affected parents (unless mutation) Trait is found in every generation Affected individuals transmit the trait to ~1/2 of their children (regardless of sex)

Autosomal dominant traits There are few autosomal dominant human diseases: Achondroplasisa Neuorfibromatosis Huntington’s Disease

X-linked recessive pedigrees Trait is rare in pedigree Trait skips generations Affected fathers DO NOT pass to their sons Males are more often affected than females Daughters of affected males are carriers (Heterozygous) Only females will be heterozygous Affected males usually born to unaffected females

X-linked recessive traits Hemophilia Muscular Dystrophy Colorblindness http://colorvisiontesting.com/ishihara.htm

X-linked recessive traits ex. Glucose-6-Phosphate Dehydrogenase deficiency hemolytic disorder causes jaundice in infants and (often fatal) sensitivity to fava beans in adults the most common enzyme disorder worldwide, especially in those of Mediterranean ancestry may confer malaria resistance

X-linked dominant pedigrees Trait is common in pedigree Affected fathers pass to ALL of their daughters Males and females are equally likely to be affected Every generation Sometimes more often in females (fatal in males) Affected sons must have affected mother Affected daughters must have affected mother or father

X-linked dominant diseases X-linked dominant diseases are extremely unusual Often, they are lethal (before birth) in males and only seen in females ex. Rett ex. X-linked rickets (bone lesions)

Y-linked expression => only found in males

Y-linked traits Male patterned baldness Hairy ears Y-chromosome infertility

Mitochondrial Inheritance Only ova have this type of DNA-- Mom’s will give to ALL kids If mom is unaffected, NO kids will be

Mitochondrial Inheritance Dysfunctional mitochondria Poor growth Loss of muscle coordination, muscle weakness, visual problems, hearing problems, learning disabilities, heart disease, liver disease, kidney disease, gastrointestinal disorders, respiratory disorders, neurological problems, autonomic dysfunction and dementia

What is the pattern of inheritance? What are IV-2’s odds of being a carrier?

Sample pedigree - cystic fibrosis What can we say about I-1 and I-2? What can we say about II-4 and II-5? What are the odds that III-5 is a carrier?

What is the inheritance pattern? What is the genotype of III-1, III-2, and II-3? What are the odds that IV-5 would have an affected son?

III-1 has 12 kids with an unaffected wife 8 sons - 1 affected 4 daughters - 2 affected Does he have reason to be concerned about paternity?

Practice 1 2 3 4 5 6 7 8 9 10 I II III

Autosomal Dominant

Autosomal Recessive

Autosomal Dominant

Autosomal Recessive

Autosomal Dominant

Sex Linked Recessive

X linked Dominant

Autosomal Dominant

Y-linked

Draw a Pedigree on your own… On a sheet of paper Isaac and Chloe have 3 kids. Omar, Sarah and Hunter: Omar and Hunter both have achondroplasisa. Sarah does not. She marries Kyle and has three kids: Phil, Rory and Beth. Rory suffers from achondroplasisa while Phil and Beth do not. Omar marries Hailey and they have 2 kids, Kameron , who has the disorder and Shawn who does not. Kameron marries Lauren, who is a dwarf and has Nathan and Jamie, neither of which are dwarfs. Hunter marries Samantha and has Joey and Bryson. Bryson is a dwarf, Joey is short, but not a dwarf. Laura marries Robert, who is a dwarf and has Mason, Covey and Erica. Mason is a dwarf and marries Julianna, who is normal size and they have Anna, normal size as well. Covy is normal sized but falls in love with his sister, Erica. They have three kids, Sean, Drew and Matt , all three of which are dwarfs. Draw a pedigree for this family, showing the name and genotype for each individual. On a scale of 1-5, how do you feel about pedigrees today?