Genetics

Chapters 4 and 5

RNA

ribonucleic acid, very similar to DNA  except is has uracil instead of thymine as a pairing base, is single stranded instead of double

Transcription

•  the process by which RNA is synthesized from a DNA template 

• The DNA of a gene is “rewritten” into being RNA and processed into mRNA

• 3 stages: initiation, elongation, termination

  • Initiation: RNA polymerase binds to a promoter site on DNA near the start of a gene

  • Elongation: enzyme goes along the DNA strand and builds a RNA strand by adding the pairs on (UACG) (A and U/T, C and G)

  • Termination: the enzyme reaches the termination sequence that signals the end of the gene, the new RNA strand is released 

• happens in the nucleus

mRNA

the RNA that has been synthesized into DNA, “messenger RNA,” result of transcription

translation

• how RNA directs the synthesis of a polypeptide 

• mRNA is "decoded" to build a protein that contains a specific series of amino acids (amino acids are building blocks for proteins)

• mRNA becomes proteins

• Happens in the ribosomes (rough endoplasmic reticulum or cytoplasm)

tRNA

•  transfer RNA, a cloverleaf shaped strand of about 80 nucleotides, 

  • Reads 3 letters at a time of the mRNA, grabs the matching amino acid and connects it to a ribosome so a functional protein can be built and used/join others

  • Reads and connects

ribosomes

make proteins by reading genetic instructions from mRNA

genotype

composition of genes, the DNA

phenotype

the outward appearance due to the genotype and environment, the observable traits and characteristics

autosomal inheritance

passed down to kids through non-sex chromosomes (on pairs 1-22) so each gender child has equal chance of inheritance

autosome

• any chromosome that is not a sex chromosome; we have 44 autosomes/22 pairs. A specific type of chromosome

• can be autosomal dominant or recessive disease

chromosome

• organized package of DNA in a cell

  • We have 46 total chromosomes (23 pairs). 44 are autosomes (22 pairs) and 2 are sex chromosomes (1 pair). 

sex-linked inheritance

traits that are passed by genes on the sex chromosomes (X and Y), men are more often affected by X linked ones bc they dont have the normal chromosome to counteract it, usually are recessive genes

carrier

has the disease allele but is phenotypically normal (they dont present it), can pass to offspring, they have Aa. for sex linked-only females can be carriers

dominant

observable characteristic, capital letter

recessive

hidden characteristic, only displayed if both recessive, lowercase letter

recurrence risk

probability that a family member will have a genetic disease in a family that is already affected. If one parent has it and is autosomal dominant but other is normal, occurrence and recurrence risks for each kid are ½.

occurrence risk

the chance a genetic condition will happen for the first time in a family

single-gene inheritance patterns

aka Mendelian inheritance, the idea of how dominant and recessive traits are passed down, or sex chromosome linked ones

Down Syndrome

• Trisomy 21, aneuploidy (has an extra), 1/800

  • Clinical presentation: mental challenges, low nasal bridge, epicanthal folds (fold that covers inner canthal of eye), flat low ears, protruding tongue, short, poor muscle tone

  • ^ risk w/ maternal age, ^ risk of congenital heart disease, respiratory infections, leukemia

Turner Syndrome

• sex chromosome aneuploidy, only have 1 X instead of 2, karyotope 45 X, always female

  • Clinical presentation: no ovaries (sterile), short, webbed neck, widely spaced nipples, many stillborns/miscarriages, coarctation/narowing of the aorta, pedal edema in newborns, sparse body hair,  

  • Usually get the X chromosome from mom and dad’s isn’t passed down/gets lost, causing this

  • Teenagers have to get estrogen (helps develop secondary sex characteristics and prevent osteoporosis)

Klinefelter syndrome

• sex chromosome aneuploidy, boy is born with at least one extra X (can have 4 extra; with each extra, abnormalities increase; can also have an extra Y) 

  • Clinical presentation: gynecomastia, small testes, sparse body hair, sterile, tall, high-pitched voice

  • 1 in 1,000 men

  • Increased risk with maternal age

Cri du chat syndrome

• aka cry of the cat, chromosomal deletion/missing piece on number 5 

  • Clinical presentation: low birth weight, mentally challenged, microcephaly, have a high-pitched mewing cry like a cat d/t larynx problems

Huntington disease

• autosomal dominant, starts showing in 30s-40s

  • Clinical presentation: nerve cells slowly break down and die, chorea, decline in movement/thinking/behavior

cystic fibrosis

• autosomal recessive, carriers are phenotypically normal, the gene makes it so ur chloride channels are defective so you get a salt imbalance that makes super thick dehydrated mucus, hurts lungs and pancreas, dont live past 40

  • Clinical presentation: malnourished bc pancreas gets plugged up, frequent bacterial infections,

neurofibromatosis

autosomal dominant, 3 types, changes the tumor suppressor genes, causes tumors to grow on nerve tissue

hemophilia

• x linked recessive, couple types, lack a specific clotting protein (factor VIII or IX deficiency) 

  • Males are affected more bc they only have one X, while females are carriers instead

duchenne muscular dystrophy

• x-linked inheritance, DMD gene is deleted so dystrophin doesnt work properly so muscle cells dont survive

  • 1 in 3500 males

  • Clinical presentation: progressive muscular degeneration, gowers sign (climbing hands up legs when getting off of floor), often have enlarged calves

incidence rate

• the number of new cases of disease reported during a specific period, usually one year, divided by the number of individuals in the population

  • More so how much it is spreading

prevalence rate

• the proportion of the population affected by a disease at a specific point in time, varies from population to population

  • More so how common it is

factors for a higher recurrence risk

more than one affected family member, the expression of the disease in the proband is more severe, the proband is of the less commonly affected sex

proband

the first person in the family with the hereditary condition, the prospitus/prospita

effect on recurrence risk of the disease is in remote relatives

recurrence risk decreases rapidly

Coronary Artery Disease (CAD)

•  talking about coronary heart disease- increases risk of MI and stroke d/t atherosclerosis 

  • Familial tendencies: ^ risk with affected relatives (^ esp females), fam hx age of onset younger than 55 years, autosomal dominant familial hypercholesterolemia

  • Environmental factors: high-fat diet, sedentary, smoking, obese

Hypercholesterolemia

autosomal dominant familial trait

Hypertension

• ^ risk of heart disease, stroke, kidney disease

  • Familial tendencies: 20-40$ of it is genetic

  • Environmental factors: important! Sodium intake, sedentary, stress, obesity

cancer

2nd leading cause of death, often follows familial patterns, environment and lifestyle has a big effect, tobacco counts for ⅓ of all cancers

colorectal cancer

2nd most common

• Familial tendencies: 2-3x^ if 1st degree relative, clusters in families, inherited adenomatous polyposis coli (APC) gene mutations play a big role in familial adenomatous polyposis, somatic mutations often involved, mutations in any of 6 genes cause hereditary nonpolyposis colorectal cancer

• Environmental factors: high-fat low-fiber diet

breast cancer

• 12% of women who live to 85 years old

  • Familial tendencies: 1st degree relative = 2x risk 

    • Recurrence risk ^ if relatives age of onset is young and if bilateral

    • autosomal dominant form makes up 5-10% related to chromosome 13 and 17 (BRCA2 and 1), makes 50-80% lifetime risk and ^ risk of ovarian cancer

diabetes

• leading cause of blindness, heart disease, and kidney failure

  • Familial tendencies: 

    • T1: (autoimmune destruction of insulin-producing beta cells), ^ risk if sibling and if diabetic dad

      • ^ risk for twins (?), associated with human leukocyte antigen class 2 alleles, insulin gene, other genes

    • T2: more common, 90% of diabetics, family hx. 

      • MZ twins hav a 90% recurrence risk, first degree relative has a risk too, certain genes, glucokinase gene

      • Most important risk factors are family hx and obesity

  • Environmental factors: T2 obesity and lack of exercise

obesity

• BMI > 30, risk for heart disease, stroke, cancer of prostate/breast/colon, T2 DM

  • BMI = kg/height in meters squared

  • Familial tendencies: body weight tends to follow parents, leptin gene and receptors

alzheimer disease

• progressive dementia and memory loss, amyloid plaques and neurofibrillary tangles, 2x risk if 1st degree relative has it, 

  • Early onset mutations: PS1, PS2, APP genes primarily cause 

  • Late onset mutations: ε2, ε3, and ε4 alleles ^ risk 2-10x

alcoholism

• 3-5x risk with alcoholic parent

  • Studies done with adopted offspring of alcoholic parents 4x risk. Adopted w/ nonalcoholic genetic parents to adoptive alcoholics did not have increased risk

  • Genes: ALDH2*2 allele = less likely, GABA allelic variation ^ risk

schizophrenia

10x risk if parent has it, if parent and sibling have it 20%^ risk, two affected parents is 50% risk, also many environmental factors

bipolar disorder

aka manic depressive disorder, risk ^ 5-10% if first degree relative, normal risk is 0.5%, also many environmental factors