Pedigree Analysis Dr. Monisha Banerjee Professor Molecular & Human Genetics Lab Department of Zoology University of Lucknow Lucknow What is a Pedigree?  A pedigree is a pictorial representation of a family history.  It is an important tool for studying inherited diseases and other traits.  Pedigree analysis uses family trees and information about affected individuals . I 1 2 II 1 2 3 4 5 III 1 2 3 4 5 6 7 8 9 5 6 IV 1 2 3 4 Most common signs and symbols used in pedigree analysis A Typical Pedigree Mating Normal I Female Normal Male 1st born II Affected Siblings Basic patterns of inheritance • Autosomal, recessive • Autosomal, dominant • X-linked, recessive • X-linked, dominant (very rare) • Y-linked Autosomal vs. sex-linked traits Autosomal traits are caused by genes on autosomes (chromosome #1- #22) e.g., we speak of autosomal recessive or autosomal dominant traits or diseases. Sex-linked traits are caused by genes on the sex chromosome (X or Y) e.g., we speak of X-linked recessive or Xlinked dominant traits or diseases. Recessive inheritance If d is the disease allele and D is normal, then only dd genotypes are affected Typically not seen in every generation Affected offspring can be born to unaffected parents Dominant inheritance If D is the disease allele and d is normal, then only dd genotypes are disease free* Dominant trait/disease found in every generation* Affected offspring never** born to unaffected parents *Assuming 100% penetrance **Assuming no new mutation Autosomal recessive Trait is rare in pedigree Trait often skips generations (hidden in heterozygous carriers) Trait affects males and females equally Autosomal recessive diseases in humans Most common ones • Cystic fibrosis • Sickle cell anemia • Phenylketonuria (PKU) • Tay-Sachs disease Autosomal dominant Trait is common in the pedigree. Trait is found in every generation.  Appears in both sexes in equal frequency. Affected individuals transmit the trait to ~1/2 of their children (regardless of sex). Autosomal Dominant disease in humans ACHONDROPLASIA (a sketelal disorder causing dwarfism) Huntington’s disease X-linked recessive Trait is rare in pedigree. Trait skips generations. Affected sons are usually born to unaffected but carrier mothers. Affected fathers DO NOT pass trait to their sons. Males are more often affected than females. Female carrier mates with normal male Sperm Fx M XNXA XNY XN Eggs XA XN Y F M XNXN XNY normal normal F M XAXN XAY carrier X-linked recessive disease affected Half* her daughters will be carriers Half* her sons will be affected X-linked recessive diseases  Hemophilia in European royalty Duchenne Muscular Dystrophy Glucose-6-Phosphate Dehydrogenase deficiency Partial pedigree analysis of haemophilia in royal families of Europe Only males develop the disease! X-linked dominant Trait is found in every generation  Affected sons must have an affected mother Affected mother if heterogygous will pass the trait to ½ of the sons and ½ of their daughters Affected fathers pass trait to ALL of their daughters Males and females are equally likely to be affected X-linked dominant disease Affected males mates with normal females FxM XNXN Sperm XAY XN Eggs XN XA Y F M XNXA XNY affected normal F M XNXA XNY affected normal • All his daughters will be affected • None of his sons will 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 eg. Incontinentia pigmenti (skin lesions) eg. X-linked rickets (bone lesions) eg. Hypophosphatemia Y-Linked Inheritance  Traits are found in every generation  Traits on the Y chromosome are only found in males, never in females.  The father’s traits are passed to all sons.  Dominance is irrelevant: there is only 1 copy of each Y-linked gene (hemizygous). Goals of Pedigree Analysis  Determine the mode of inheritance: dominant, recessive, partial dominance, sex-linked, autosomal, mitochondrial, maternal effect.  Predict the risk of disease in future offspring in a family (genetic counseling). Thank you