genetics exam three

pedigrees

used for uncontrollable crossing, ex. long-lived, rare and few offspring species (humans)

pedigree symbol

circle = female, square = male, shaded = displaying, dot/shaded = carrier, deceased = line

twin pedigree symbols

consanguinity

mating between individuals who share a recent ancestor, increases likelihood of inheriting same allele from both parents

rareness in pedigrees

if a condition is rare, anyone marrying into the family does not have condition

phenylketonuria

autosomal recessive condition caused by mutations in PAH gene, toxic to brain, can be maintained (need for low phenylalanine)

autosomal recessive traits

¼ of all children affected, can skip generations, affects males and females

autosomal dominant traits

passed down through both sexes, cant skip generations, affected child has an affected parent (unless spontaneous), unaffected parents do not transmit

x-linked recessive trait

affected sons come from unaffected heterozygous mothers, affected males pass allele to all daughter

x-linked dominant trait

both males and female affected

y-linked traits

every related chromosomal male has it

dizygotic twins

2 eggs fertilized with two different sperm (genetically distinct)

concordant

both members of a twin pair have a trait

monozygotic twins

single egg fertilized by single sperm followed by splitting of embryo during early development (genetically identical)

discordant

only one member of the pair have a trait

concordance

percentage of twin pairs that are concordant for a trait

genetic testing

screens for known traits, based on population membership, for conditions

types of screening

ultrasound, amniocentesis, newborn screening, presymptomatic testing, pharmagogenetic

genetic material

contains complex information, replicates, encodes phenotype, can vary

DNA

has chromosomes, composition is the same throughout the organism, stable

Griffith experiment

1928, transformation in bacteria streptococcus pneumoniae, injected bacteria into mice to see if it would live or die

avery macleod and mcCarty experiment

questioned what the transforming factor was, found that it was DNA

hershey - chase experiment

provided additional support for DNA as genetic material with bacteriophage T2

nucleic acids

nucleotides, phosphate group, five carbon sugar and cyclic nitrogen-containing compound called a base

nitrogenous bases

purine (two rings): adenine, guanine
pyrimidine (one ring): cytosine, thymine, uracil

methylated DNA

affects expression of gene, turns it on or off

secondary structure of DNA

two strands form double helix, sugar-phosphate backbone with phosphodiester bonds, hydrogen bonds in-between bases, anti-parallel and complementary

RNA structure

nucleotides connected with phosphodiester linkage, single-stranded, uracil instead of thymean, ribose sugar has an 2’ OH

chargaff rule

A = T and G = C (purine = pyrimidine)

x-ray diffraction

shows structure of DNA, from rosalind franklin

nobel peace prize

founded by nobel, given for science, no more than three winners, given to watson, crick and wilkins for DNA structure

DNA double helix

righthanded, spiral, sugar-phosphate backbone, held together by H-bonding, 10 base pairs per turn, base pairs stacked 0.34 nm apart, 2nm diameter to helix, B form

B-DNA

physiological DNA, most common form, right-handed, 10 nt/turn, 1.9 nm wide

A-DNA

high salt/dehydrated, condensed (shorter and wider), 11 nt/turn, 2.3 nm wide

Z-DNA

GCGCGCG repeating, role in expression and tension reduction, left handed, 12 nt/turn, 1.8 nm wide

major vs minor groove

major groove is bigger and minor is smaller

RNA secondary structure

hairpin structure formed from single strand nucleotides invert and are complementary

H-DNA

three-stranded (triplex) DNA, formed when DNA unwinds and one strand pairs with double-stranded DNA from another part, in long sequences of only purines/pyrimidines, in mammalian genomes

central dogma

founded by Crick, DNA → pre-mRNA → mRNA → Protein

packaging of DNA

human genome is 6 billion bp, 2 meters in length, has supercoiling

Supercoiling

overwound (+ supercoiling): more than 10 bp/turn
underwound (- supercoiling): less than 10 bp/turn (most common)
easy to pull apart and pack

topoisomerase

adds or removes turns to DNA helix

eukaryotic packing

DNA associated with histones (protein) create chromatin

euchromatin

uncondensed, on chromosome arms, many unique genes, can be transcribed and has crossing over

heterochromatin

more condensed, at centromeres and telomeres, repeated sequences, few genes, no transcribing and no crossing over

chromatin

complex of DNA and proteins

histones

positively charged basic proteins, 20-30% arginine and lysine, highly conserved amino acid sequence

non-histone chromosomal proteins

negatively charged, large heterogenous group of proteins, acidic, structural and regulatory and motor, play big role of regulating transcription

five types of histones

H1, H2a, H2b, H3, H4 (complex with DNA to form a nucleosome)

nucleosome

basic unit of structure of chromatin, histone octamer (2 of each histone type), ~ 150 bp of DNA

chromatosome

nucleosome plus histone H1, bound at site where DNA enters and exists octamer, locks DNA into place

length of DNA that wraps around histone proteins

core DNA = 145 - 147 bp, linker DNA = 50 bp

model for nucleosome structure

DNA wraps around histone octamer 1.7 times, tails are positively charged amino acids (can be modified to change structure of chromatin)

polytene chromosomes

repeated rounds of DNA replication without cell division, thousand of DNA copies side by side

chromosome puff

regions that have localized swelling, relaxed chromatin, transcriptionally active

DNase I sensitivity

open chromatin structure, correlates with transcription (structure changes course of transcription)

histone modifications

alters binding of DNA to histone, acetylation that increases transcription + other methods like methylation and phosphorylation

DNA modification

methylation of bases, retained through DNA replication and cell division, not a mutation

centromere

DNA at constricted region in metaphase chromosomes, site of attachment of kinetochore where spindle fibers bind

telomere

prevents end to end joining, protects from degradation by nuclease, end of DNA

centromere structure

large (lots of bp), heterochromatin, repeated DNA, have CenH3 histone,

telomerase

enzyme that adds repetitive sequence that forms protective loops on ends of chromosome, has built-in RNA template

telomere sequence

hexameric, 5’ - TTAGG - 3’ and 5’ - CCCTAA - 3’

c-value

amount of DNA per cell, increase with complexity of organism

genome size differences

larger genomes have more repetitive DNA,

moderately repetitive DNA

150-300 bp length, thousands of copies, tRNA and rRNA genes

unique sequence DNA

one or few copies per haploid genome, 25 - 50% of the DNA, mostly protein-coding genes

tandem repeat sequences

short DNA sequence repeat over and over, positioned one after another and found in clusters

interspersed repeat sequences

scattered throughout genome, either short or long

SINES

short interspersed nuclear elements, less than 500 bases

LINES

long interspersed nuclear elements, thousands of base pairs,

highly repetitive DNA

short, 10 bp or less, millions of copies, not transcribed often, “satellite DNA” since less dense

denaturation of DNA

caused by high temps that break H bonds, higher G + C content needs higher temp to denature

melting temperature

temperature at which ½ the DNA molecular are in the single stranded state

renaturation of DNA

slow cooling, base pairs reform

hybridization

complementary single stranded DNA from different sources form base pairs

somatic mutations

affects body cells

germ-line mutations

affects sex cells and can be passed on

point mutations

one for one changes in DNA or RNA sequence

transitions

change in nucleotide but not class, 2x more common

transversions

change in chemical class, purine to pyrimidine

synonymous point mutation

change in nucleotide sequence does not cause change in poly peptide

nonsynonymous point mutation

change in nucleotide sequence causes change in polypeptide

point mutation disorder

sickle cell anemia (single transversion)

frameshift mutation

insertion or deletion, often causes more problems

Tay - Sachs

frameshift mutation that causes gene to build up toxic chemicals in brain

mutations in non-coding regions

intron is not a problem, promotor sequence is a problem

cause of mutation

breakdown or misreplication of DNA, ionizing radiation, mutagens

tautomeric shifts

changes pairing rules, G and T, A and C, spontaneous

thymine dimers

UV light crosslinking adjacent thymines in DNA and kinks it, causes 1-base deletion

intercalating agents

small plate-like molecules that fit between rungs in DNA ladder, causes 1-bp insertions if present during replication