2. Clinical Genetics - Winroth

• X-linked recessive - female is only carriers

  • criss-cross inheritance = affected male has unaffected daughters

  
• x-linked dominant

  • both parents transmit mutation
  • male to only daughters
  • female to half son and daughter
• Y linked traits pass from father to son only
• multifactorial disorder

  • does not follow a clear inheritance pattern - maybe caused by genes and exogenous factors (environment)
• concordant - twins have the same disease
• discordant - twin with one one twin affected
• sickle cell - concordant disease (both twin affected)
• type 1 DM - multifactorial disorder

  • disease concordance is less than 100% in MZ twins = nongenetic factor plays a role
• Recurrence risk (RR) increases as the closeness of the relationship to the proband increases
• RR increases as the number of affected relatives increases
• Recurrence risk (RR) increases as the severity of the disorder increases
• RR in multifactorial inherited disorder increases as the consanguinity of the mating partners increases.
• Congenital heart defect

  • multifactorial in origin
  • heart problem may run in the family but may not get the same disorder
• When the proband is female or young, there is likely to be a greater genetic contribution to MI in the family
• schizophrenia

  • evidence of genetic contribution
  • 22q11 deletion
• T1 DM - alleles linked to HLA-DR3 and HLA-DR4

  • altered immune response to environmental antigen = leads to destruction of pancreatic beta cells