Section 14-2:Human Genetic Disorders

From Molecule to PhenotypeThere is a direct link between genotype and

phenotypeExample:

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

Disorders Caused by Individual GenesSickle 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 capillariesCan result in damage to cells, tissues, organs

Disorders Caused by Individual GenesCystic fibrosis (CF)

Most common among people of European ancestryMost 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

Disorders Caused by Individual GenesCF 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

Disorders Caused by Individual GenesHuntington’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 unknownSymptoms 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

Genetic AdvantagesWhy 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

Chromosomal DisordersUsually caused by

nondisjunctionCreates gametes

with an abnormal number of chromosomes

Chromosomal DisordersIf 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

Chromosomal DisordersNondisjunction of X chromosomes can lead to

Turner’s syndrome, where a woman only inherits one X chromosome

Called a monosomySex organs do not develop properly at

puberty, sterile, small/short stature, high voice

Karyotype: 45, XO

Chromosomal DisordersNondisjunction can also cause a male to

inherit an extra X chromosomeDisorder called Klinefelter’s syndromeAlso sterileKaryotype: 47, XXY