bio 10

• Genetics of Inherited Diseases
• Genetic diseases


  Often caused by mutations
• Mutations


  Changes in the DNA sequence that are often associated with disease

  
• The inheritance of many human genetic diseases can follow a Mendelian inheritance pattern
• Mutations

  Changes in the DNA sequence that result in an allele that confers disadvantage or disease

  
• Recessive mutations


  Only expressed if a person inherits two bad alleles

  
• Dominant mutations


  Expressed in a person even when present in one copy

  
• Carriers


  Individuals who are heterozygous for a recessive disease
• Sickle-cell anemia


  Malformed red blood cells take on a sickle crescent shape, leading to blood clots, strokes, heart attacks
• Sickle-cell anemia


  Caused by a change in one nucleotide in a single gene called SCA on chromosome 15

  
• Sickle-cell anemia


  Recessive condition
• Gaucher disease


  Caused by mutation in a gene called GBA on chromosome 1, leading to buildup of fatty acids and progressive degradation
• Gaucher disease


  Recessive condition
• Huntington's disease


  Neurodegenerative disease caused by a mutation in only one copy of the HTT gene, leading to dementia, loss of inhibition, and loss of motor function

  
• Autosomal dominant diseases


  How could a single mutant copy of a gene cause a disease?

  
• Exceptions to Mendelian Genetics in Humans
• Sex-linked alleles


  Alleles on the sex chromosomes

  
• Polygenic traits


  Two or more genes involved in phenotype
• Complex traits


  Influenced by both environment and genetics, e.g. diet, exercise
• Sex-linked inheritance


  Traits determined by genes on the sex chromosomes

  
• Sex determination in humans

  Females carry 2 X chromosomes, males carry one X and one Y

  
• Sex-linked inheritance of diseases

  Females can be homozygous or heterozygous, males only carry one copy of the X chromosome

  
• Sex-linked diseases


  • Red-green colour blindness, hemophilia, Duchenne muscular dystrophy
• Eye colour


  Influenced by alleles in as many as ten different genes, difficult to predict genetically
• Complex traits


  Influenced by both genetic and environmental risk factors
• Complex traits


  • Genetic predisposition to alcohol abuse, type II diabetes
• Psychiatric disorders


  Schizophrenia, major depressive disorder, bipolar disorder, autism, juvenile schizophrenia, schizoaffective disorder
• Schizophrenia


  Adult onset, characterized by disorganized thought, delusions, hallucinations, and disorganized speech
• Schizophrenia


  46% of identical twins diagnosed together, 70% of cases are sporadic, 30% have a family history
• Schizophrenia


  Clinical diagnosis, not biological, may be explained by Mendelian inheritance, new mutations, or gene-environment interactions
• Environmental factors for schizophrenia

  • Time spent in urban environment/minority population
  • Viral infections at or near birth
  • THC usage/exposure
  • Vitamin D exposure
  • Early childhood abuse
• Autism spectrum disorder


  Clinical spectrum of diagnoses ranging from mild cognitive impairment to syndromic mental retardation, majority of severe cases caused by new mutations in many different genes
• Human Pedigree Analysis
• Pedigrees

  Visual aids to track inheritance of genetic traits through 2 or more generations

  
• Pedigrees

  • Widow's peak trait
  • Attached earlobe trait
• Autosomal recessive traits

  Traits controlled by gene loci on autosomal chromosomes, inherited in a recessive manner

  
• Carriers


  Individuals that do not express a recessive trait but have a heterozygous genotype

  
• Autosomal recessive pedigree


  Offspring of 2 affected parents will always be affected, affected offspring can have 2 unaffected parents, trait can skip generations, males and females equally affected

  
• Autosomal recessive traits


  • Albinism
• Recessive genes in molecular biology

  What type of gene would act recessively?