PEDIGREE CHARTS A family history of a genetic

PEDIGREE CHARTS A family history of a genetic condition © 2007 Paul Billiet ODWS

What is a pedigree chart? • Pedigree charts show a record of the family of an individual • They can be used to study the transmission of a hereditary condition • They are particularly useful when there are large families and a good family record over several generations. © 2007 Paul Billiet ODWS

Studying human genetics • You cannot make humans of different types breed together • Pedigree charts offer an ethical way of studying human genetics • Today genetic engineering has new tools to offer doctors studying genetic diseases • A genetic counsellor will still use pedigree charts to help determine the distribution of a disease in an affected family © 2007 Paul Billiet ODWS

Symbols used in pedigree charts • • • Normal male Affected male Normal female Affected female Marriage A marriage with five children, two daughters and three sons. The eldest son is affected by the condition. Eldest child Youngest child © 2007 Paul Billiet ODWS

Organising the pedigree chart • A pedigree chart of a family showing 20 individuals © 2007 Paul Billiet ODWS

Organising the pedigree chart – Generations are identified by Roman numerals I II IV © 2007 Paul Billiet ODWS

Organising the pedigree chart • Individuals in each generation are identified by Arabic numerals numbered from the left • Therefore the affected individuals are II 3, IV 2 and IV 3 I II IV © 2007 Paul Billiet ODWS

Today. . . Pedigree analysis v In humans, pedigree analysis is an important tool for studying inherited diseases v Pedigree analysis uses family trees and information about affected individuals to: vfigure out the genetic basis of a disease or trait from its inheritance pattern vpredict the risk of disease in future offspring in a family (genetic counseling)

Today. . . Pedigree analysis v How to read pedigrees v Basic patterns of inheritance vautosomal, recessive vautosomal, dominant v. X-linked, recessive v. X-linked, dominant (very rare) v Applying pedigree analysis - practice

Sample pedigree - cystic fibrosis male female affected individuals

Autosomal recessive traits • Trait is rare in pedigree • Trait often skips generations (hidden in heterozygous carriers) • Trait affects males and females equally

Autosomal recessive diseases in humans v Most common ones • Cystic fibrosis • Sickle cell anemia • Phenylketonuria (PKU) • Tay-Sachs disease v 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 • Trait is found in every generation • Affected individuals transmit the trait to ~1/2 of their children (regardless of sex)

Autosomal dominant traits v There are few autosomal dominant human diseases (why? ), but some rare traits have this inheritance pattern ex. achondroplasia (a sketelal disorder causing dwarfism)

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

X-linked recessive traits ex. Hemophilia in European royalty

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 recessive traits ex. Glucose-6 -Phosphate-Dehydrogenase deficiency

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

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. incontinentia pigmenti (skin lesions) ex. X-linked rickets (bone lesions)

Pedigree Analysis in real life: complications Incomplete Penetrance of autosomal dominant traits => not everyone with genotype expresses trait at all Ex. Breast cancer genes BRCA-1 and BRCA-2 & many “genetic tendencies” for human diseases

Pedigree Analysis in real life: complications Sex-limited expression => trait only found in males OR females

Pedigree Analysis in real life Remember: • dominant traits may be rare in population • recessive traits may be common in population • alleles may come into the pedigree from 2 sources • mutation happens • often traits are more complex • affected by environment & other genes

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 can we say about gene frequency?

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?

Breeding the perfect Black Lab How do we get a true-breeding line for both traits? ? black individuals = fetch well grey individuals = don’t drool