Chapter 14: Human Inheritance

1. Chapter 14: Human Inheritance Section 14-2: Human Genetic Disorders

2. From Molecule to Phenotype • There is a direct link between genotype and phenotype • Example: • People of African or European descent are more likely to have wet earwax (dominant) while those of Asian or Native American ancestry have the dry form (recessive) • The difference is in ONE BASE in the gene for a membrane-transport protein - a change from a G to an A • Changes in a gene’s DNA sequence can change proteins by altering their amino acid sequences, which may directly affect one’s phenotype

3. Disorders Caused by Individual Genes • Sickle Cell Disease • Caused by defective allele for beta-globin, part of hemoglobin • Makes hemoglobin less soluble, molecules stick together when blood’s oxygen level decreases • Molecules clump into long fibers, forcing cells into a sickle shape that are more rigid than normal RBCs, and they • Tend to get stuck in the capillaries • Can result in damage to cells, tissues, organs

4. Disorders Caused by Individual Genes • Cystic fibrosis (CF) • Most common among people of European ancestry • Most cases result from the deletion of just 3 bases in the gene for a protein called cystic fibrosis transmembrane conductance regulator (CFTR) • Amino acid phenylalanine is missing from the protein • CFTR normally allows chloride ions (Cl−) to pass across cell membranes - the removal of phenylalanine causes the protein to misfold, and it is destroyed

5. Disorders Caused by Individual Genes • CF con’t • Tissues malfunction because cell membranes can’t transport Cl- • Children with CF have serious digestive problems and produce thick, heavy mucus that clogs their lungs and breathing passageways • People with one normal copy of the CF allele are unaffected by CF, because they can produce enough CFTR to allow their cells to work properly • Two copies of the defective allele are needed to produce the disorder – it is recessive

7. Disorders Caused by Individual Genes • Huntington’s disease • Caused by a dominant allele for a protein found in brain cells • Allele contains a long string of bases in which the codon CAG (glutamine) repeats over and over again – more than 40X • Reason why is unknown • Symptoms of Huntington’s disease do not appear until middle age - mental deterioration and uncontrollable movements • The greater the number of codon repeats, the earlier the disease appears, and the more severe are its symptoms

8. Genetic Advantages • Why are alleles for sickle cell disease or CF still around if they can be fatal for those who carry them? • Individuals with one sickle cell allele are resistant to malaria • Individuals with one CF allele have a harder time developing typhoid fever

9. Chromosomal Disorders • Usually caused by nondisjunction • Creates gametes with an abnormal number of chromosomes

10. Chromosomal Disorders • If 2 copies of an autosome do not separate, a person can be born with 3 copies of that chromosome – known as trisomy • The most common form of trisomy is Down syndrome (trisomy 21) • Mild to severe mental retardation and a high frequency of certain birth defects

11. Chromosomal Disorders • Nondisjunction of X chromosomes can lead to Turner’s syndrome, where a woman only inherits one X chromosome • Called a monosomy • Sex organs do not develop properly at puberty, sterile, small/short stature, high voice • Karyotype: 45, XO

12. Chromosomal Disorders • Nondisjunction can also cause a male to inherit an extra X chromosome • Disorder called Klinefelter’s syndrome • Also sterile • Karyotype: 47, XXY