Beruflich Dokumente
Kultur Dokumente
Learning Objectives
1. 2. 3. 4. 5. 6. Definitions used in practice of medical genetics Mode of inheritance: single gene and polygenic inheritance Symbols of a pedigree (family tree) Construct a pedigree Determine patterns of Mendelian inheritance Mention examples of Mendelian inherited disorders.
Pedigree Study
Why study the family tree (pedigree)
Transmission of a trait in a family Its frequency among relatives Determine the mode of inheritance
Pedigree symbols
Mendelian Inheritance
Caused by a particular genotype at one locus (Single Gene Trait) Autosomal or Sex chromosome linked Dominance and Recessiveness (refers to characters and not genes)
DOMINANT TRAIT: expressed in a heterozygote RECESSIVE TRAIT: expressed only in homozygote CARRIER:Heterozygous individual carrying a mutant allele. He/She is phenotypically normal but can transmit the mutant allele to his/her offspring. HEMIZYGOUS: males have a single gene on each locus on the X and Y chromosome
An affected person usually has at least one affected parent Vertical Transmission Affects either sex Transmitted by either sex (Pedigree) Homozygotes are rare usually present with a more severe phenotype. Regulatory proteins of complex metabolic pathways or key structural proteins Genetic Risk: A child of an affected parent has a 50% chance of being affected (Punnetts square 1)
Pedigree of AD
Examples of AD disorders
Nervous System: Neurofibromatosis
AD diseases
Familial Hypercholestrolemia
Skeletal AD disorders
Examples of AD disorders
Urinary: polycystic kidney GIT: familial adenomatous polyposis Hematopoeitc: Hereditary sherocytosis Metabolic: familial hypercholestrolemia Skeletal: Marfan Syd, and Achondroplasia
Pedigree of AR
X-Chromosome Inactivation
Lyon Hypothesis One X chromosome is active in the cells of the females due to dosage compensation Intra-uterine random inactivation Females are actually mosaics
Barr Body
Affects mainly males Affected males are usually born to asymptomatic carrier mothers and usually have affected male relatives (Pedigree) Females are affected if the father is affected and the mother is a an asymptomatic carrier or due to skewed X-inactivation Genetic risk: Affected males never transmit the trait to their sons but all his daughters are obligate carriers who can then transmit the trait to 50% of their sons, thus showing a diagonal transmission (Punnetts square 3,4)
DMD
Fragile X-Syndrome
Y-Linked inheritance
Affects only males All affected males have an affected father Genetic risk: transmitted to all sons of the affected male Example: hairy ears, azospermia (infertility)