DNA & Genetics

DNA Replication Errors and Mutations

• Error rates– in bacteria 3 errors per 100,000 bases copied

– every generation of cells would have 1,000 faulty proteins

• Proofreading and error correction– after DNA polymerase replicates strand, a smaller polymerase

proofreads it and makes corrections

– results in only 1 error per 1,000,000,000 bases copied

• Mutations - changes in DNA structure due to replication errors or environmental factors– some cause no effect, some kill cell, turn it cancerous or cause

genetic defects in future generations

DNA Function

• Serves as code for protein synthesis, cell replication and reproduction

• Gene - sequence of DNA nucleotides that codes for one polypeptide

• Genome - all the genes of one person

Translation of mRNA Flow Chart

DNA & Peptide Formation

Cell Cycle

• G1 phase, the first gap phase

– normal cellular functions

• S phase, synthesis phase– DNA replication

• G2 phase, second gap phase

– preparation for mitosis• replicates centrioles, synthesizes enzymes for cell division

• M phase, mitotic phase– nuclear and cytoplasmic division

• G0 phase, cells that have left the cycle

Functions of Mitosis

• Embryonic development • Tissue growth• Replacement of old and dead cells• Repair of injured tissues

Mitosis: Prophase

• Chromatin supercoils into chromosomes

• Nuclear envelope disintegrates

• Centrioles sprout microtubules, mitotic spindle

• Centrioles move to poles

Metaphase Chromosome

Mitosis: Metaphase

• Chromosomes line up on equator• Spindle fibers attach to centromere• Asters anchor centrioles to plasma membrane

Mitosis: Anaphase

• Centromeres divide• Spindle fibers pull sister chromatids to opposite

poles of cell

Mitosis: Telophase

• Chromatin uncoils

• Nuclear envelopes form

• Mitotic spindle breaks down

Cytokinesis

• Division of cytoplasm

• Myosin pulls on actin in the membrane skeleton

• Causes crease around cell equator called cleavage furrow

• Cell pinches in two

Timing of Cell DivisionCells divide when:

• Cells large enough

• DNA replicated

• Adequate supply of nutrients

• Growth factor stimulation

• Open space in tissue

Cells stop dividing when:

• Loss of growth factors or nutrients

• Contact inhibition

Cancer

• Tumours– abnormal growth, when cells multiply faster than they

die– oncology is the study of tumors

• Benign– connective tissue capsule, grow slowly, stays local – potentially lethal by compression of vital tissues

• Malignant– unencapsulated, fast growing, metastatic (causes 90%

of cancer deaths)

Causes of Cancer

• Carcinogens - estimates of 60 - 70% of cancers from environmental agents – chemical

• cigarettes, food preservatives

– radiation• UV radiation, particles, rays, particles

– viruses• type 2 herpes simplex - uterus, hepatitis B - liver

Mutagens• Trigger gene mutations

– cell may die, be destroyed by immune system or produce a tumor

Defenses against mutagens• Scavenger cells

– remove them

• Peroxisomes – neutralize nitrites, free radicals and oxidizing agents

• Nuclear enzymes– repair DNA

• Tumor necrosis factor (TNF) destroys tumors

Cancer Genes• Oncogenes

– mutated form of proto-oncogenes – sis oncogene causes excessive production of growth

factors• stimulate neovascularization of tumor

– ras oncogene codes for abnormal growth factor receptors

• sends constant divide signal to cell

• Tumor suppressor genes– inhibit development of cancer– damage to one or both removes control of cell division

Effects of Malignancies

• Displaces normal tissue, function deteriorates– rapid cell growth of immature nonfunctional cells

– metastatic cells different tissue origin

• Block vital passageways– respiratory or vascular

• Diverts nutrients from other tissues– tumors have high metabolic rates

– causes weakness, fatigue, emaciation, infection

Chromosomes

• Karyotype– chart of chromosomes at metaphase by size, structure

• Homologous chromosomes– 2 chromosomes in each pair, 1 from each parent

– autosomes (22 pairs)

– sex chromosomes (X and Y)

• Germ cells - sperm and egg cells, haploid• Somatic cells - all other cells, diploid

Genes and Alleles• Gene loci

– location of gene on chromosome

• Alleles– two homologous chromosomes have same gene at

same locus, may be different forms of gene

• Dominant allele– produces normal, functional protein

• Recessive allele– when both alleles are recessive produces abnormal

protein or no protein

Genetics of Earlobes• Genotype

– alleles for a trait (DD)

• Phenotype– trait that results

• Dominant allele (D)– expressed with DD or Dd– Dd parent ‘carrier’ of

recessive gene

• Recessive allele (d)– expressed with dd only

Punnett square

Multiple Alleles, Codominance, Incomplete Dominance

• Gene pool– collective genetic makeup of whole population

• Multiple alleles– more than 2 alleles for a trait– such as IA, IB, i alleles for blood type

• Codominant– both alleles expressed, IAIB = type AB blood

• Incomplete dominance– phenotype intermediate between traits for each allele

Polygenic Inheritance

• 2 or more genes combine their effects to produce single phenotypic trait, such as skin color

Pleiotropy

• Single gene causes multiple phenotypic traits, as in sickle-cell disease

Sex-Linked Inheritance

• Recessive allele on X, no gene locus for trait on Y, so hemophilia more common in men

Penetrance and Environmental Effects

• Penetrance– % of

population to express predicted phenotype

• Role of environment– brown eye

colour requires phenylalanine from diet to produce melanin, the eye pigment

Alleles at the Population Level

• Dominance and recessiveness of allele do not determine frequency in a population

• Some recessive alleles, blood type O, are the most common

• Some dominant alleles, polydactyly, are rare

Recombinant DNA Technique