Pedigree analysis


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A review of the section and why we use pedigree analysis to address genetic diseases in humans.

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Pedigree analysis

  1. 1. Pedigree Analysis
  2. 2. Classical Genetics• Mendelian inheritance describes inheritance patterns that obey two laws – Law of segregation – Law of independent assortment• Simple Mendelian inheritance involves – A single gene with two different alleles – Alleles display a simple dominant/recessive relationship
  3. 3. • Consider, for example, the traits that Mendel studied Wild-type (dominant) allele Mutant (recessive) allele Purple flowers White flowers Axial flowers Terminal flowers Yellow seeds Green seeds Round seeds Wrinkled seeds Smooth pods Constricted pods Green pods Yellow pods Tall plants plants• Another example is from Drosophila Wild-type (dominant) allele Mutant (recessive) allele Red eyes White eyes Normal wings Miniature wings
  4. 4. • Human genetic diseases caused by recessive mutant alleles – The mutant alleles do not produce fully functional proteins
  5. 5. Lethal Alleles• Essential genes are those that are absolutely required for survival – The absence of their protein product leads to a lethal phenotype • It is estimated that about 1/3 of all genes are essential for survival• Nonessential genes are those not absolutely required for survival• A lethal allele is one that has the potential to cause the death of an organism – These alleles are typically the result of mutations in essential genes – usually recessive, but can be dominant
  6. 6. Lethal Alleles• Many lethal alleles prevent cell division• Some lethal allele exert their effect later in life – Huntington disease • Characterized by progressive degeneration of the nervous system, dementia and early death • The age of onset of the disease is usually between 30 to 50• Conditional lethal alleles may kill an organism only when certain environmental conditions prevail – Temperature-sensitive (ts) lethals • A developing Drosophila larva may be killed at 30 C • But it will survive if grown at 22 C
  7. 7. • Every gene carries information telling the body how to make a particular protein. – Adult cells have two copies of each gene. – If one copy of the gene doesn’t work, the cell has a backup.• New versions of genes can be produced by mutations – These new alleles can produce proteins that either • Do not work • Or do something they’re not supposed to• Thus any condition associated with this is referred to as a genetic disease
  8. 8. • Cystic fibrosis (CF) – A recessive disorder of humans – About 3% of caucasians are carriers – The gene encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) • The CFTR protein regulates ion transport across cell membranes – The mutant allele creates an altered CFTR protein that ultimately causes ion imbalance • This leads to abnormalities in the pancreas, skin, intestine, sweat glands and lungs
  9. 9. Example: Cystic fibrosisThe cell membranes of the cells lining the lungs and airpassages contain CF membrane proteins Cl- Cl- Cell membrane Cl- CF membrane proteins Cl-The CF protein pumps chloride ions from one side of themembrane to the other
  10. 10. The CF protein produces a higher concentration of chlorideions on one side of the membrane than the other Cl- H2O Cl- Cl- Cl- H2O Cl- H2O Cell membrane Cl- H2O H2O Cl- H2OWater molecules follow the chloride ions across the semi-permeable cell membranes by… …osmosis.
  11. 11. The body uses the CF chloride pump to move water intosecretions like the mucus found in the trachea and sweat.If your cells cannot make working chloride pumps, yourmucus becomes too thick and sticky due to lack of waterHowever, to make a functioning chloride pump, each cellonly needs one good copy of the gene for it.So, cystic fibrosis is recessive
  12. 12. c CDefective gene Healthy geneproduces non-working produces workingchloride pump chloride pump Cl - Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- This individual does not suffer from cystic fibrosis, but is a carrier
  13. 13. Neither copy of thegene carried by thisindividual can c cproduce a workingchloride pump Cl- Cl- Cl - Cl- Cl- This individual will Cl - Cl- Cl- suffer from cystic Cl- Cl- fibrosis REMEMBER: Genes do NOT exist to cause disease… … defective genes cause disease
  14. 14. Pedigree Analysis• In the study of human traits, there are not controlled parental crosses• Rely on information from family trees or pedigrees• Pedigree analysis is used to determine the pattern of inheritance of traits in humans
  15. 15. Pedigree SymbolsFigure 2.10
  16. 16. Pedigree Analysis• Pedigree analysis is commonly used to determine the inheritance pattern of human genetic diseases• Genes that play a role in disease may exist as – A normal allele – A mutant allele that causes disease symptoms• Disease that follow a simple Mendelian pattern of inheritance can be – Dominant – Recessive
  17. 17. • A recessive pattern of inheritance makes two important predictions – 1. Two normal heterozygous individuals will have, on average, 25% of their offspring affected – 2. Two affected individuals will produce 100% affected offspring• A dominant pattern of inheritance predicts that – An affected individual will have inherited the gene from at least one affected parent – Alternatively, the disease may have been the result of a new mutation that occurred during gamete formation
  18. 18. Figure 2.10