Genetic Variation Flashcards
Beta Globin: 3 allele
A, S, C
remember beta globin is Part of what makes up hemoglobin (2 betaglobin, 2 alphaglobin)
A allele
Normal
o GAG
o Glutamic acid
o HbA: 2 A alleles (in both b-globin subunits, 1 in each b-globin subunit)
S Allele
o GUG
o Valene
• HbS: 2 S alleles (1 in each b-globin subunit)
C Allele
o AAG
o Lysine
• HbC: 2 C alleles
SA
o Some sickle shaped cells o Mild form of blood disease o Beneficial b/c provides partial protection against severe malaria o May have shortened life span o Will have affects of anemia o Heterozygous
CC
o More protected from malaria
o Very mild form of anemia
o Doesn’t require medical treatment
SS
o Seveerly affected by Sickle Cell anemia
o S allele encodes for collapse, two of them means you make only sickle cell shaped cells
Emphysema
o Alpha1 antitripson gene
• Makes enzyme to bind to elastase
• Inhibits elastase
Elastase
• Break down elastin and keep perfect balance between old and new elastin
Nondisjunction
is the failure of a pair of chromosomes to separate during anaphase of cell division.
can occur in as many as 10% of meotic divisions
major cause of spontaneous abortion
Emphysema (More)
onset in middle age
shorten life 10-30 yrs
can probably pass to offspring (b/c late onset)
Emphysema Phase 1
Environmental Interaction
o Ciggaretes affect action of enzyme mentioned
• Affect inhibition of protein who breaks down elastin
• Too much elastin break down
• Loss of lung elasticity→ emphasema
Emphysema Phase 2
o Mutant form of alpha1antitripson genes • Pis allele mutated • Enzyme has lower affinity for elastase • Doesn't bind it as it should • Doesn't inhibit it right • Decrease lung elasticity→ emphesema
Oogenisis
• Go through meosis I, wont resolve meiosis II until much later
o Developing egg cells in limbo
o Imporoper connection of microtubules to centrosomes
• Bad pulling
• Because eggs spending more time in limbo stage
Beneficial Mutations
• Reduction of succeptibility to HIV
o env region in HIV genome encodes surface glycoprotein
o glycoproteins on surface of virus interact with and be accepted by CD4 surface protein AND CCR5 co-receptor to get access to the cell
what version of CCR5 co-receptor you have determines succeceptibility
CCR5 Alleles
• Homozygous for normal CCR5: succeptiable to HIV
• Heterozygous for delta 32 mutation: delay in progression of AIDS by 2 years
• Homozygous for delta 32 mutation: reduced ability of HIV to infect cell
o PROBABLY NEVER GET AIDS
Delta 32
deletion of 32 nucelotides: 1 nucelotide short of deleting 11 amino acids and keeping the rest in frame o SHIFTING CODING FRAME o Premature stop o Truncated CCR5 protein o Cant be recognized by virus
Why Delta 32?
• Probably in the past conferred resistance to black plague and small pox
o So increased frequency of delta 32 in Europe
Variable Number of Tandem Repeats (VNTR)
regions that help identify us at the genetic level
• DNA fingerprinting
• Based on variable number of tandem repeats
• About 30 base pairs long
• Number is variable 6, 10, 30, 40 whatever
• PCR to amplify that region of the genome
• PCRing produces bands of different lengths
o Size will differ based on number of repeats
• One band: 2 copies of same allele
• 2 different bands: different alleles (heterozygous)
• Need to amplify hundreds of regions of genome
Restriction Fragment Length Polymorphism (RFLP)
• Another way to fingerprint
• Restriction enzymes
o cut DNA at specific nucleotide sequence
• Restriction enzyme recognizes a sequence, makes a cut
• Things that aren’t restriction enzyme sequences aren’t cut
• Probe to detect fragments
o Load into gel, run it out
o Long band migrates more slowly
• Transfer using Southern Blot to membrane
• Probe membrane
o Probe recognizes thingy
• When blob recognized, can determine genotype
• Homozygote AA
o 1 band
• Heterozygote: 2 bands
o No cut in S
• SS genotype: 1 band
Copy Number Variation (CNV)
• Tandem repeats
• Copies
• Or Deletion
• Genotype microarrays
o Useful for detaching copy number variation, differences among indivs in number of copies region of genome
o CNV: large and can include 1+ complete genes
CVN Genotyping
• Fluresnce technology • probes: o amylase gene (starch break down) o Populations with high starch diets, o Have lots of copies of analyase gene • A whole extra one compared to non high starch diet
Single Nucleotide Polymorphism (SNP)
Look at SNPs across indivs in a pop, where are they different at SNPs?
• Eye color
o Look for associations between alleles and pheonotypes
Just Correlation
Eye Color SNPs
o C-G allele: Blue Eyes
o T-A allele: Brown Eyes
o THESE GENES ARE NOT IN THE ACTUAL GENE FOR MELANIN MAKING COLOR. They are downstream
o 94% with CG had blue eyes, only 2% had brown eyes
o Down stream, is associated with expression of melanin gene
o CG downstream, decreased expression of melanin, blue eyes
o TA downstream, normal melanin expression, brown eyes
Nondisjunction in Meiosis I
• both homologous chromosomes migrate to same pole
• daughter cell has 2 copies of a chromosome, should only have one
• Gametes: none are good, two have an extra version of a chromosome
• Two are missing completely a chromosome
o Most likely no viable gametes
o But sometimes you can produce viable offspring (the ones with extra
Nondisjunction in Meiosis I results
o 2 gametes with extra copy of chromosome
• trisomy
o 2 games lacking chromosome (monosomy)
o Down syndrome
Nondisjuntion in Meiosis II
o Pulls both copies two one side
• 2 good gametes
• 1 missing the chromosome
• 1 with an extra copy of the chromosome
XXX
o : not a big deal
o X inactivation
o Only genes on 1 X are being expressed anyway
XYY
o Ok, not much on Y chromosomes anyway
slightly taller people
XXY
Kleinfelter o Tall o More feminine features o Small testes No normal X inactivation
X
Turner Short o neck and skin webbing o poor breast development o cant have children • poorly developed ovaries
Polyploid Organisms
• many fetuses that go spontaneous abortion
o triploid or tetraploid (3 or 4 complete sets of chromosomes) eggs
• defective spindle apparatus
Nondisjunction Results out of 10000 births
o 8000 have major chromosomal abnormalities
o 7500 spontaneous abortion
o 500 live births
Extra or Missing Chromosomes in Live Births
Trisomy 21: three copies of 211
• 1 of 155 live born childen have chromosome abnormality
• down syndrome most common
o trisomy 21 or 47, +21 (47 insread of 26 b/c of extra in 21)
• trisomy 13 and 18
o only live about 1 year
Translocations
Bits of chromosomes that are swapped to different chromosomes
