Genetics Test 2 Flashcards
Monogenic traits
expressivity and penetrance
Polygenic traits
variance
Monogenic
One gene contributes to phenotype
Polygenic
More than one gene contributes to a genotype e.g. eye color and height.
Penetrance
does genotype show or not for a person
Expressivity
in a population does a gene vary in expression
Compound Heterozygous
2 different mutant alleles -Compound heterozygosity reflects the diversity of the mutation base for many autosomal recessive genetic disorders
Hemizygous
1 gene w/ only 1 allele –e.g. Males for X chromosome genes
Proband/Propositus/Index Case
The person who draws our attention to the family..affectet
Consultand
The person consulting a geneticist
Compound Heterozygousity Examples
Tay-Sachs disease. In addition to its classic infantile form, Tay Sachs disease may present in juvenile or adult onset forms, often as the result of compound heterozygosity between two alleles, one which would cause the classic infantile disease in homozygotes and another that allows some residual HEXA enzyme activity.[6]
Sickle cell syndromes. A variety of sickle cell disorders result from inheritance of the sickle cell gene in a compound heterozygous manner with other mutant beta globin genes. These disorders include sickle cell-beta thalassemia.[7] In the case of sickle cell anemia, an individual with one allele for hemoglobin S and one allele for hemoglobin C would still develop the disease, despite being heterozygous for both genes.[8]
de novo (sporadic) mutation
a newly formed mutation (parents are WT)
Isolated
parents are carriers of a rare gene. their child develops inherits disease
Degrees of Relation to Proband
1st degree relatives: Parents/Siblings/Children of Proband (or other)
2nd degree: Grandparents, Grandchildren, Aunts, Uncles, Nieces/Nephs
3rd degree: 1st cousins, 4th degree 1st cousins, once removed
Autosomal Dominant
Auto Recessive
X or Sex Linked Recessive
X Linked Dominant
Y Linked
Allelomorphy
changing of allele expression
What affects allelomorphy?
–Penetrance: Does a trait show or not? Measured in %
•= #affected/#withAffectedGeneotype
–Expressivity: how well an allele is expressed
(qualitative)
–envir, genes, and epigene factors; above two are also
affected by these three
co-dominance
In genetics, codominance is a phenomenon in which a single gene has more than one dominant allele
A condition in which both alleles of a gene pair in a heterozygote are fully expressed
–Red (homo-dom) pink (het) white (homo-rec)
Neurofibromatosis, type 1:
Age Dependent Penetrance and
Variable Expressivity. A Dominant Loss of Function.
Penetrance:
some may never develop disease or only at a certain age.
Expressivity:
varies from patches to tumors. 50% cases are de novo, to find out if sporadic or isolated
genotype the parents.
Split-Hand Deformity
Auto-Dom often has reduced penetrance
And therefore skips generations
Genetic heterogeneity
at least two alleles create
similar or same phenotype
divided into: locus heterogeneity, allelic heterogeneity, and cliincal heterogeneity
Locus Heterogeneity
alleles from two genes cause a
phenotype/ mutation at a different gene causes a similar phenotype
e.g. epistasis Myo7A, Harmonin,
Cadherin 23 all disrupt Steriocilia in retina causing
Usher Syndrome 1.
For example, retinitis pigmentosa has autosomal dominant, autosomal recessive, and X-linked origins. However, only one mutant locus is needed for the phenotype to manifest.
Allelic heterogeneity
allelomorphy-alleles at same
location (gene) cause phenotype
different mutations at the same locus causes a similar phenotype.
For example, β-thalassemia may be caused by several different mutations in the β-globin gene.
Clinical Heterogeneity (phenotypic heterogeneity)
penetrance and expressivity
mutation within the same gene causes a different phenotype.
Common Recessive=Dom.
Incomplete Penetrance
Variable Expressivity
Paternal Imprinted Auto Dom
Maternal Imprinted Auto Dom
X Linked, Dom Hemis Abort
X Linked Inbred “M to M”
Novel Mutation
Explanations of Consanguinity
• The Westermarck Effect-not liking people you were
raised in close proximity to. BUT, 1st and 2nd cousins
tend not to experience WE.
• Women tend to prefer males with alleles in common to
their father’s Human Leukocyte Antigen/MHC. Men
with 2-7 alleles in common are preferred.
• 2nd order and above relatives…We tend not be raised in
close proximity/and they resemble us in ways that may
contribute to mate choice.
Calculating Inbreeding Coefficient
(1/2)^n x (1+F)
n= number of individuals involved in the path
F= inbreeding coefficient for the common ancestor
http://pawpeds.com/pawacademy/genetics/genetics/inbreeding.html
Polygenic Phenotypes
•To many genes we stop using Mendel and look at Means,
Variance and Standard Deviation of “Normal Distribution” (a
graph of Observations)
Mean
= Average
Variance
= A Groups Total Average Distance
from Mean
measures how far a set of numbers is spread out. (A variance of zero indicates that all the values are identical.)
Standard Deviation
= Range we find 68%
(called 1 SD) of data points, 95% (is 2SDs),
99.7% (is 3SDs)
A measure of the dispersion of a set of data from its mean. The more spread apart the data, the higher the deviation.
Variance Equation
_Sum of (each value-mean)^2_ # of values – 1
*Answer in X units squared
Heritability Equation
Gene Variance/Total Variance
Standard deviation Equation
Square Root of Variance
*Answer in X units
–Shows us the width of the curve at around the mean
where 68%, 95% and 99.7% of data is included
Falconer Threshold
Hypothesis
Child 1 of Diseased Parents is more likely to
acquire a disease than Child 2 of Undiseased
Parents of a population if the disease is at all
genetic.
Less overlap of graphs = greater genetic influence on the disease = lesser
environmental influence
Falconer postulated the existence of a threshold. Embryos whose susceptibility exceeds a critical threshold value develop cleft palate; those whose susceptibility is below the threshold, even if only just below, avoid cleft palate. (polygenic)
Quantitative Traits
polygenic, continuous
Variation like height, skin color or Crop Yield
Qualitative Traits
The trait is there or it’s not
Hardy Weinberg Requirements
–Large Population
•Prevents Genetic Drift-change in allele freq. due to:
–Bottle Neck Effect eg. Killing off of homozygous people
–Founder Effect eg. Pickett’s infamous African Diaspora
–Genetic drift leads to “Fixation” allele freq.=100%
–Random Mating
–No Mutations
–No Natural Selection
–No immigration into population (No Genetic Flow)
Hardy Weinberg
•Hardy Weinberg Distribution- Occurs when alleles freq
is constant = No occuring evolution
•Failure to meet regulation means allele freq has changed
and evolution has occurred.
Hardy Weinberg Equations
p + q = 1
–p = % Dominant alleles (A) in population
–q = % of recessive alleles (a) in population
p2 + 2pq + q2 = 1
–p2 = # AA individuals
–2pq = # Aa individuals
–q2 = # aa individuals
HW Practice
•Population N=100 Cows
•What is your Dominant allele freq?
•How many heterozygous brown cows do you
have?
–you have 64 white cows & Black = B White =b
Practice work/answer
- q^2 = 64/100 = .64
- q = .80
- p = -q – 1 = .80 -1 = .20
- Dominant allele freq = .20
- Brown cows = 2pq
- 2 x .20 x .80 = 32 brown cows
Gene Position and Orientation: A and B are…
A and B are In Coupling Orientation
Gene Position and Orientation: a and b are…
a and b are In Coupling Orientation
Gene Position and Orientation: A and B are ________ to a and b
A and B are In Repulsion to a and b
A is ______ to B, a is ______ to b
A is ‘In Cis’ to B, a is ‘In Cis’ to
b
A is _______ to b AND to a
B is _______ to a AND to b
A is ‘In Trans’ to b AND to a
B is ‘In Trans’ to a AND to b
Recombination
-The Exchange of Genetic Material By
Homologous Chromosomes During Meiotic Prophase.
-Changes the Cis-Trans Orientation
Recombinant Chromosomes are __________, Because the Parent
Does Not Have This _________________.
Recombinant Chromosomes are Non-Parental, Because the Parent
Does Not Have This Cis-Trans Orientation.
Which progency are recombinants and which are not?
“_________” recombination is genetically detectable
“Non-sister” recombination is genetically detectable
“___________” recombination is NOT detectable
“Sister-sister” recombination is NOT detectable
Alleles of 2 Unlinked Genes
F1 X F1
9:3:3:1 Dihybrid Ratio
Weaker linked genes recombine more
Decreasing parental haplotypes= Less Parental and more Recombinant
Gamete Frequencies
More like dihybrid cross (cross between F1 offspring (first-generation offspring) of two individuals that differ in two traits of particular interest. For example, BB × bb)
Alleles of Linked Genes
Ratio Moves Toward 3:1
Stronger linked genes do not
recombine as often, keeping
Parental haplotypes together
= More Parental and Less
Recombinant Gamete Frequencies
More like Monohybrid cross (mating between individuals who have different alleles at one genetic locus of interest)
Measuring Genetic Linkage Violates__________________ because…
Measuring Genetic Linkage Violates Mendel’s Law of Independent Assortment because
Multiple genes move as one unit (like single gene)
Calculations: θ
•Recombination Fraction (θ) – recombs/total chances to
recomb
***Two are basically the same thing in the end:
•θ = r = total of both recombinants
Calculations: r
•Frequency of Gametic Recombination (r) – recomb
gametes/total gametes
***Two are basically the same thing in the end:
•θ = r = total of both recombinants
Recombinants Calculation
λ1 + λ2 = r (total recombinants)
–assuming recombinants are equal (they should be)
Chances of 1 recomb to happen Calcuations
= r
–= ½ r X ½ r = chances receiving two recombinants
Challenges of Mapping Human
Genes
- Each couple makes only few babies
- Cis-Trans orientation hard to determine from pedigree
- Diseases are usually rare
- Overall we do not have much data to work with
Log of Odds Ratio (LOD)
= How we decide a
rare disease is linked or not linked
The LOD score compares the likelihood of obtaining the test data if the two loci are indeed linked, to the likelihood of observing the same data purely by chance. Positive LOD scores favor the presence of linkage, whereas negative LOD scores indicate that linkage is less likely.
Likely linked > 3……..-2 > Likely Independently Assorted
***Requires we know Cis-Trans Orientations (Phase Known)
LOD Calculation
LOD Phase-known Calculation Example
LOD phase known
•Because LODs are Logs they are additive
–This way we can add data from different
families and create a statistical pool of data for a
disease.
–When the pool total becomes >3 we can say the
disease is linked
–When less than -2 we can say it’s independently
assorted
LOD score for Phase Unknown
Mapping Issues: Recombination Hotspots
Recombination is not uniformly distributed
along a chromosome. But usually broadly enough distributed.
However there is a tendency for linked genes to be inherited as
haplotypes and so hotspots can tend to cluster alleles of linked genes
Mapping Issues: Multipoint Mapping
Mapping using many molecular markers and the
disease allele can provide higher resolution. Many markers have been
mapped against each other and placed on the sequence map…so they
form a useful marker framework to position new loci. Three point
mapping is very powerful because in humans flanking double
recombinants on a dense marker map are extremely rare.
Mapping Issues: Exclusion Mapping
Rare recombinants in small families can be very
powerful tools despite low contribution to Z. With dense marker maps
a recombination breakpoint can provide the “maximal physical extent”
of a genetic locus.
