A document to record ancestry, used by genealogists in study of human family lines, and in selective breeding of other animals
Pedigree
Why is human genetics hard to follow?
-a small number of offspring
-experimental crosses not ethical
-long generation time (22-23 yrs)
..
What are the 4 basic inheritance patterns?
-Autosomal recessive
-Autosomal dominant
- Sex-linked recessive
-Sex-linked dominant
-2 unaffected parents can have affected offspring
-both male and female offspring affected at similar freq.
Autosomal recessive
What are examples of autosomal recessive disorders?
-cystic fibrosis (severe damage to lungs)(causes thickened fluids)
-Sickle cell anemia (affects shape of blood cell)
-Tay-Sachs (toxic build up in brain and spinal cord)
-Affected individuals have at least 1 affected parent
-Affected parent of either sex can pass on to offspring of either sex
-appears in male and female
- not sex linked
Autosomal dominant
-unaffected parents can have affected offspring
-Males affected more frequently than females
-Transmitted from mothers to sons
-50% of child will be affected
Sex-linked recessive
Example of__________
Sex-linked recessive
color blindness is___linked and affects _____more than _______
-x
-male
-female
-affected offspring come from parents
-males pass only to daughters
-females pass to children of either sex
-if dad is affected 100% of daughters are affected
-if mom affected 100% of sons are affected
Sex-linked dominant
What are examples of sex-linked dominant disorders?
-Alport syndrome
-Coffin-Lowry syndrome
-Fragile X syndrome
-Incontinentia pigmenti
-Vitamin D resistant rickets
-only males have it
-pass to all sons, none of daughters
Y-linked trait (dominant)
-Mothers always pass on
-Fathers never pass on
Mitochondrial mutation
What is the chance of their next child being affected?
(a)= affected
(1/2) x (1/2)= (1/4)
-gender x condition
Look at slide 34 in Ch 6. pt 1
DO IT NOW
-non identical twins
-2 zygotic eggs
Dizygotic twins
-identical twins
Monozygotic twins
-the trait shared by the members of a twin pair
-genetically the same
-environment may be similar
-the increased rate is more likely impacted by genetic factors rather than environmental factors
concordant traits
-separate embryotic sacks
dizygotic twinning
-comes from 1 zygote
-early splitting
Dichorionic diamniotic (monozygotic twinning)
-late split
Monochorionic diamniotic (monozygotic twinning)
-very late split
-same sack
Monochorionic monoamniotic (monozygotic twinning)
Overweight biological parents tend to have_______children. There is no ___ _____ between the weight of children and that of their adoptive parents.
-overweight
-consistent association
This is an example of :
A pregnant woman is concerned about
exposure to an environmental substance (drug, chemicals, or virus)
that cause birth defects.
Environmental impact
Genes on the same chromosomes tend to
get transmitted together
certain combinations of alleles are passed more frequently than others
linkage
Complete linkage leads to;
____% non recombinant gametes and progeny
100
the crossing over between ______ chromosomes can break linkage
homologous
Alleles are passed in different combinations from how they were inherited
Recombination
Recombination leads to:
-recombinant gametes and progeny
________ associated with physical change in chromosomes
recombinant phenotypes
recombinant diagram
When a plant is normal with tall leaves and short with dwarf leaves, they are
nonrecombinant progeny
This is an example of
no crossing over
This is an example of:
which results is;
crossing over
-2 nonrecombinant and 2 recombinant gametes
One chromosome contains both wild-type alleles, one chromosomes contains both mutant alleles
coupling (cis configuration)
wild type allele and mutant alleles are found on the same chromosomes
repulsion (trans configuration)
Usually 2 step process:\
1. determine data are consistent with genes assorting independently (chi-squared test)
2. If the data is not consistent with independent assortment, this suggests genes are linked
- determine how closely linked the genes are
determining genetic distance
How to calculate recombination frequency
recombination freq.=(# of recombinant progeny/ total # of progeny)x100%
No correlation between which alleles are transmitted=50% , recombinant gametes =50cM
independent assortment
Two genes are linked if they are less than____ apart
50cM
If the progeny resulted in:
-66
-77
-28
-33
Which are recombinant, and what would the distance be?
-66 and 77 are the highest number= parental progeny
-28 and 33 lowest numbers= recombinant progeny
(28+33)/(66+77+28+33)=0.303 x100= 30.3 cM
a crossover at one place on the chromosome reduces the likelihood of a second crossover
interference
How to calculate amount of interference:
coefficient of coincidence= observed DCO/expected DCO =
-((2)^3)/(total amount of flies x DCO freq.)
-((2)^3)/12= 0.67
Distances based on crossover/linkage
genetic map
Distances based on actual base-pair differences
physical map
This is an example of
crossovers with three linked loci
recombination distance are ______accurate the larger they get
less
Consider the mutation and cross over
How halotype works
consider how when the top of loci is blue, it shows the blue parents trait
Quantitative trait locus mapping (QTL)
-controls have little to no genes of the condition
-lower freq. of variant
-variant linked to condition
-cases have the condition
Genome-wide association studies (GWAS)
Used to assign a gene to a particular human chromosome
-gene present (given)
-Human chromosomes present ( find most similar to gene presented)
Somatic-cell hybridization
displays the mutant phenotype
displays the wild type
-prepared from cells halted in metaphase(relaxed)
- numbered based on size
-Sex chromosomes
-based on haploid # (23 chromosomes)
Karyotyping
With sex chromosomes, the largest is the ___ chromosome and the short chromosome is the ___ chromosomes
-X
-Y
-moving, gaining, or losing pieces of a chromosome
-2n=6
-duplication
rearrangement
-changes in # of copies of an individual chromosome
-2n+1=7
-trisomy
Aneuploidy
-extra whole set of chromosomes
-3n=9
-autotriploid
polyploidy
Types of rearramgement:
-duplication
-deletion
-translocation
-inversion
Copied region of chromosomes
duplication
deleted region of chromosomes
deletion
inverting (flipping) region of chromosomes
inversion
moving part of chromosome somewhere else
translocation
-bulge during pairing in meiosis 1
Duplication (segment of chromosome is duplicated)
-formation of loop during pairing in prophase 1
Deletion
-turned 180 degrees
inversion
Inversion that doesn't include the centromere
paracentric inversion
inversion includes the centromere
pericentric inversion
If a crossover were to occur in the inverted region,
it would result in a complication
The packaging of tremendous amounts of genetic info. into the small space within a cell has been called
The ultimate storage problem
Is overwound or underwound causing it to twist on itself
Supercoiling DNA
-add two turns
- occurs when DNA is overrotated; the helix twists on itself
Positive supercoil
-removes 2 turns
-occurs when DNA is underwound; the helix twists on itself in the opposite directions
Negative supercoiling
What do these charactericstics describe?
-less condensed
-on chromosome arms
-unique sequences
-many genes
-throughout S phase
- often transcription
- crossing over is common
Euchromatin
What do these characteristics describe?
-more condensed
-At centromeres, telomeres, and other specific places
- repeated sequence
-Late S phase
-infrequent transcription
-crossing over is uncommon
Heterochromatin
Regions of relaxed chromatin where active transcription is taking place
chromosome puffs
Chromosome puffs on giant polytene chromosomes isolated from the __ ____ of larval Drosophila
-salivary glands
Chromosome fragments that lack ______ are lost in mitosis
centromeres
Proposes that mitochondria and chloroplasts in eukaryotic cells arose from bacteria
Endosymbiotic theory
endosymbiotic theory
Organelles in a ______cell segregate randomly into the progeny cells.
heteroplasmic
understand it
What is the importance of mutations?
-provides raw material for evolution
-source of many diseases and disorders
-look at whats wrong when we alter a gene
-Do not get passed on to the offspring
-passed to new cells through mitosis creating a clone of cells having mutant gene
Somatic mutations
-reproductive cell mutations
-passed on
-meiosis and sexual reproduction allow mutation to be passed down to about half the members of next generation
germ-line mutation
One letter is replaced by another
base substitution
A to G & C to T (purines switch with purines) (pyrimidine switches with pyrimidine)
Transition
A or G to C or T (purines switch with pyrimidines) (pyrimidine switch with purines)
Transversion
Frameshift mutations are not_____by 3
divisible
in frame insertions and deletions are divisible by
3
Original sequence:
GGG AGT GTA GAT CGT
What would the sequence look like if a base substitution were to occur on the following nucleotide?
Original sequence:
GGG AGT GCA GAT CGT
What would the sequence look like if a base insertion were to occur on the following nucleotide?
Original sequence:
GGG AGT GTT AGA TCG T
What would the sequence look like if a base deletion were to occur on the following nucleotide?
Repetitive sequence can cause______ of strands during replication
slippage
Dna polymerase adds
more repeats
unequal cross over misaligns
homologous chromosomes
The new codon encodes a different amino acid; there is a change in amino acid sequence
Missense mutation
The new codon is a stop codon; there is a premature termination of translation
Nonsense mutation
The new codon encodes the same amino acid; there is no change in amino acid sequence
Silent mutation
a mutation that hides or suppresses the effect of another mutation
Ex: wild type has red eyes (A+B+), and a mutation causes white eyes (A-B+). This allows for a fly with (A-B-) to have red eyes even if it has two mutant phenotypes.
Suppressor mutation
Second mutation in the same gene "fixes" problem caused by first mutation
intragenic
second mutation in a different gene. "fixes" the problem caused by the first mutation
Intergenic
Purines and pyrimidine bases exist in different forms called
tautomers
____ _____ pairings can occur as a result of the flexibility in DNA structures
EX: T and G binding (wobble)
C and A protonated wobble
Nonstandard base
____ base pairing leads to a replication error
Wobble
____ and ____may result from strand slippage
-insertions
-deletions
____ _____ over produces insertions and deletions
unequal crossing over
loss of purine
Depurination
loss of an amino group
deamination
Used to identify chemical mutagens
Ames test
A___ can result in possible wobble mispairing
bulge
Many incorrectly inserted nucleotides that escape proofreading are
corrected by mismatch repair
Changes nucleotides back into their original structures
Direct repair
A damaged base can be removed by______, and ______ cleaves the deoxyribose sugar.
-DNA glycosylase
-AP endonuclease
DNA _______ adds a new nucleotide and is then sealed by DNA _____ to restore the original sequence.
-polymerase
-ligase
base excision
Removes bulky DNA lesions that distort double helix
Nucleotide-excision
Can cause chromosomal rearrangement
transposons
example of transposons causing rearrangement
How to calculate the frequencies of observed genotypes?
-# of individuals with genotype divided by total # individuals
f(AA)=
f(Aa)=
f(aa)=
-f(AA)= # of AA individuals/#of total individuals
-f(Aa)= # of Aa individuals /# of total individuals
-f(aa)=# of aa individuals /# of total individuals
A population of 868 individuals has 482 AA individuals, 213 Aa individuals, and 173 aa individuals. What are the frequencies of each genotype?
f(AA)= 482/868=0.555
f(Aa)= 213/868=0.245
f(aa)= 173/868=0.199
How to calculate observed allelic frequencies
-# copies of alleles divided by total # alleles
f(A)=
f(a)=
-f(A)=(2 x #AA individuals + #Aa individuals)/(2 x total # of individuals)
-f(a)=(2 x #aa individuals + #Aa individuals)/(2 x total # of individuals)
A population of 868 individuals has 482 AA people, 213 Aa people, and 173 aa people. What are the frequencies of each allele?
-f(A)= (2 x 482 +213)/(2 x 868)=0.678
-f(a)= (2 x 173 + 213)/(2 x 868)=0.322
What does p and q stand for in this equation?
p+q=1
-p: dominant
-q: recessive
equation 1 is used to determine___
p+q=1
equation 2 is used to determine___
p^2+2pq+q^2=1
-frequencies of alleles in population
-frequencies of genotypes in the population
What are the Hardy-Weinberg Equilibrium Assumptions ?
-no selection
-no mutation
-no gene flow
-random mating
-infinite population size
0.000625 Caucasians suffer from cystic fibrosis an autosomal recessive disease.
(1)What is the frequency of the disease-causing allele in the population?
(2) find value of p
(3)What proportion of individuals are carriers?
-(1) q^2 =0.000625, q=√0.000625 =0.025
-(2) p+q=1 -> p=1-0.025= 0.975
-(3) 2pq= 2 x 0.975 x 0.025 = 0.049 , about 5% carry the cystic fibrosis mutation
in cats, all-white is dominant over colors other than all white. In a population of 100 cats, 19 are all white. Assuming that the population is in HArdy-Weinburg equilibrium, what is the frequency of the all-white allele in this population?
How many white cats would be expected to be genotype AA? Aa?
-white =19 out of 100, so 81 of the cats are not white(recessive)
-81/100 = q=0.9
-p=1-0.9 = 0.1 are white and dominant
Can cause severe changes in allelic frequencies and are more severe in smaller populations
Genetic drift
Will alter the genotype frequencies, but not the allele frequencies of a population
nonrandom mating
A tendency of like individuals to mate
-creates more homozygotes then expected
-flies with same eye color mate
Positive assortative mating
A tendency of unlike individuals to mate.
-creates more heterozygotes than expected
-fly with red eyes mates with white eyes
Negative assortative mating
-increases the likelihood of getting two copies of the same allele from the same ancestor
results in more homozygotes
inbreeding
a measure of how likely it is that two alleles are identified by descent
inbreading coefficient (F)
What is this an example of?
Alleles identical by descent
What is this an example of?
alleles identical by state
The more inbreeding the less
heterozygotes
Caused by accumulation of harmful recessive alleles
Inbreeding depression
What equations are needed when calculating with inbreeding factors?
f(AA)= p^2 + Fpq
f(Aa)=2pq-2Fpq
f(aa)= q^2 +Fpq
What will the genotype frequencies be after 1 generation of random mating, followed by 1 generation of inbreeding between siblings?(F=0.25)
p=0.6 q=0.4
Fpq= 0.25 x 0.6 x 0.4=0.06
F(AA)= p^2 =0.6^2=0.36 +0.06= 0.42
F(Aa)= 2pq= 2 x 0.6 x 0.4=0.48 -(2 x 0.06) =0.36
F(aa)=q^2=0.4^2=0.16 + 0.06 = 0.22
-Doesn't change allele frequencies by itself but changes distribution of who has them
-more homozygous
-recessive alleles that are not good will more likely show
non-random mating
Individuals from one population entering another population
migration
The amount of change in allelic frequency due to migration between populations depends on
the difference in allelic frequency and the extent of migration
changes in allele frequency due to different levels of fitness (ability to survive and reproduce)
Natural selection
One allele is always more fit than the other
-the more "fit" allele increases in frequency
Directional selection
The heterozygote is more fit than either homozygotes
-stable equilibrium reached and both alleles remain in population
Overdominance (heterozygote advantage)
Heterozygote is less fit than either homozygotes
-unstable equilibrium reached- one allele will eventually win
Under dominance (heterozygote disadvantage)
What will be the allele frequncies at the time reproduction beings ?
1. divide by the most fit number in this case 180
AA=180/180=1
Aa=162/180= 0.9
aa= 36/180= 0.2
2. A=(180+180+heterozygote)/(2x total number of individuals)
(180 + 180 +162) / (162+180+36) x 2= 0.69
a= (36 +36+ 162) / (756)= 0.31
w11<w12>w22 is an example of what?
-overdominance
w11<w12<w22 is an example of ?
Directional selection against incompletely dominant allele A1
w11>w12>w22 is an example of?
Directional selection against incompletely dominant allele A2
w11=w12<w22 is an example of?
directional selection against dominant allele A1
w11=w12>w22 is an example of
directional selection against recessive allele A2
consider this when looking at distributions