8.8- 8.10: Genetic Defects

Point Mutations:

single nucleotide changes that can result in frameshift, transition, transversion, forward, and backward mutations (see section 9.9 DNA Mutations).

Frameshift mutation

• Base pair inserted into sequence, that shifts how codons are read

Transition mutation

Purine to purine or pyrimidine to pyrimidine conversion

Transversion Mutation

• Purine to pyrimidine

• Pyrimidine to purine

Forward Mutation

Changes wild type to a mutant allele (ex mouse from one tail to two tails)

Backward Mutation

Reverse mutation that changes mutant allele back to wild type allele

Nondisjunction:

when chromosomes fail to separate during mitosis, meiosis I, or meiosis II.

Mitotic nondisjunction:

sister chromatids fail to separate → daughter cells will have an extra or missing chromosome.

Mosaicism:

occurs in cells that undergo mitotic nondisjunction or nucleotide mutations during embryonic development. A fraction of the body’s cells will have genetic abnormality.

Meiotic nondisjunction:

results in gametes with missing or extra chromosomes 

Aneuploidy:

• when organism or cell has an abnormal number of chromosomes.

  • Monosomy: only one copy of a chromosome.

  • Trisomy: three copies of a chromosome (e.g. Trisomy 21 = Down Syndrome). 

Chromosomal Breakage:

a physical break in a chromosome which can result in aberrations

Chromosomal Aberrations:

physical changes to segments of DNA. 

Karyotyping: .

the process of visually examining an organism’s set of chromosomes with a microscope to identify physical chromosome abnormalities (e.g. trisomy 21, Turner syndrome). • Performed during metaphase. Allows chromosome number, size, and shape to be analyzed

Cancer:

disease characterized by uncontrolled, abnormally dividing cells. Proto-oncogenes and tumor-suppressor genes work together to help prevent cancer.

Proto-Oncogenes:

stimulate normal cell growth and division (e.g. ras gene).

Oncogene:

mutated proto-oncogene which overstimulates cell division and causes cancer.

Tumor-suppressor genes:

suppress excessive cell growth (e.g. p53 gene). - Can mutate to decrease tumor suppression activity, contributing to cancer formation.

Cancer-Causing Agents:

1. Viruses

2. Mutagenic Agents

Viruses:

insert genetic information into the genome and disrupt the genes responsible for regulating normal cell growth, allowing cancer to develop.

Mutagenic agents:

include radiation, carcinogenic compounds, and certain infectious agents. Compounds can be used to prevent unregulated cell growth: colchicine (prevents mitotic spindle formation) and chemotherapeutic agents. 

Autosomal dominant conditions

Huntington’s Disease, achondroplasia 

Autosomal recessive conditions

Phenylketonuria, cystic fibrosis, Tay-sachs, sickle-cell anemia 

Sex-linked recessive conditions

Hemophilia, color blindness, Duchenne’s muscular dystrophy 

Chromosomal (aneuploidy) disorders

Down syndrome, Turner’s syndrome, Klinefelter’s syndrome 

Extranuclear Inheritance:

Mitochondria and chloroplasts have their own extranuclear genome.

Mitochondrial DNA i

s maternal because all of an embryo’s mitochondria come from the mother’s egg → all mitochondrial related diseases/mutations are maternally inherited.

Lethal Genes:

prevent survival of an organism. Can be dominant, recessive, or conditionally expressed.

Maternal Effect Genes:

genes which when mutated in the mother, cause a phenotypically normal mother who produces mutant offspring, regardless of offspring genotype. (e.g. defective mRNA or proteins in egg cell leads to a disrupted embryonic environment).