Genetics Exam 3 Flashcards
heterogeneous trait
a trait that can arise from a mutation in any number of DIFFERENT genes (also known as genetic heterogeneity)
complementation test
determine if mutations that cause the same phenotype are in the same or different genes
how do you test if a phenotype is due to mutations in two different genes or different mutations in the same gene?
cross affected individuals & observe phenotype with a complementation test
complementation (+)
mutations are in two different genes
ex: two parents with a “mutant” phenotype produce normal progeny-happens because the two parents have defects in DIFFERENT genes
what is the difference between heterogeneous traits and incomplete penetrance?
heterogenous involves more than one gene (two genes)
incomplete penetrance involves one gene
non complementation (-)
mutations are in the same gene
ex: offspring have the same mutant phenotype as parents. Parents have defects in the same gene: the phenotype will be expresed
what can complementation tests reveal?
can reveal the minimum number of genes that contribute to a trait (look for pairs)
epistasis
two (or more) genes that are both involved sequentially in a pathway in producing a particular pathway
what can happen as a result of epistasis?
one genotype can mask the expression of the other genotype, leading to different ratio of progeny than one would expect (9:3:4)
Which gene is epistatic?
the gene that masks the other one is the epistatic gene
what do nurse cells do in invertebrates?
deposit mRNA and proteins into the cytoplasm of the egg before the egg is released and fertilized
maternal effect genes
the phenotype of the progeny is determined by the mother’s genotype –the genotype of the father does not affect this particular phenotype of the offspring
where is most developmental genetics carried out?
in non-mammalian systems because can mutagenize animals so they produce offspring with lots of mutant phenotypes
- can then determine by looking at phenotype what kinds of genes were mutated & what their normal function are
- study what those genes are responsible for
- create model systems for studying human developmental disorders
loss of function mutations (lf)
m/+ has normal phenotype
half of the normal amount of product is enough for normal function; the animal has to be lacking both copies for a phenotype to be seen
- almost always recessive
gain of function mutations (gf)
m/+ has a mutant phenotype
the presence of the altered product (from the mutated copy) is enough to change the phenotype
-almost always dominant
often changes the function of the protein such that it has a new function or an altered function
three fundamental laws of development
- Timing is everything
- Location, location, location
- Both the above are true
an embryo is comprised of cells that are genetically all the same, but these cells end up doing different things later. how?
cells must acquire positional information to contribute to that body plan of an organism
What are the two molecular mechanisms that define positioning?
signaling & cytoplasmic factors
two types of cytoplasmic inheritance
mitochondrial inheritance
maternal inheritance
mitochondrial inheritance
mitochondria are only passed from affected mothers to all offspring (mitochondria are only passed along from the mother b/c sperm contributes no cytoplasm to egg)
-severity frequently related to the proportion of mutant mitochondria inherited at birth
maternal inheritance
maternally contributed mRNAs and proteins are critical for early developmental events of many embryos such factors are deposited into the egg during oogenesis, thus present even before cell division begins
maternal effect genes
the genes that produce these mRNAs and proteins critical for early developmental events of many embryos
maternal effect genes in mammals?
not existent because they are placental animals so the embryo uses its genes from the start and relies on mom for nutrients
maternal effect genes in non-mammalian animals?
externally deposited eggs so the mother puts into the egg proteins and RNA that the egg needs for the first few hours. embryo uses its genes only later
the axes of invertebrates is determined by…
maternally contributed mRNAs and proteins
exploratory genetics
mutagenize organisms, look for phenotype of interest, determine nature of mutation, map location of gene (first)
manipulative genetics
(can only do if you already know the identity of the gene)
knock out gene, over express gene, analyze what controls expression, etc 2nd
homeotic genes
confer positional information of the early embryo ultimately result in activation of this set of genes
what do homeotic genes do?
determine the identity of different regions all along the body axis & is CONSERVED across all organisms
-encode transcription factors & contain a “homeobox” region
homeobox region
encodes the homeodomain
Hox gene expression in ALL organisms
the order of the genes expression, from anterior to posterior parallels the order of genes on the chromosome
epigenetics
inherited changes in gene function that cannot be explained by differences in the DNA sequence
3 examples of epigenetics
- maintenance of the state of a gene (transcriptionally off or on) through many cell divisions in development through meythlation
- Imprinting
- X inactivation
Imprinting
inactivation of certain genes in male or female germline
X-inactivation
in mammalian dosage compensation
inactivation of an X chromosome through methylation and long non coding RNA
methylation
methylation of cytosine bases in DNA of developmentally important genes, primarily in the promoter region
-only cytosines in CG di-nucleotides become methylated
how is methylation maintained?
through replication by enzymes that recognize the methylated state of these cytosines
is DNA methylation distributed evenly?
not distributed evenly, tend to be in promoter regions
methylation prevents transcription
CpG islands
stretches of CGs that are methylated (60-80%)
detecting methylation
treatment with sodium bisulfate: unmetylated cytosines are converted into uracil.
compare treated vs. untreated and any methylated C will still be a C after treatment
Genomic imprinting
a specialized example of methylation
methylation occurs during the production of gametes
maternally imprinted gene
methylated (inactivated) in the production of oocytes
paternally imprinted gene
methylated (inactivated) in the production of sperm
imprinting maintenance
is maintained throughout the somatic cells of the new individual BUT is erased and then re-initiated with gametogenesis so for an imprinted gene, everyone (male & female) has one copy that is methylated and one that is not
how many imprinted genes are required for normal function?
only one copy of the gene is required for normal function, and the other copy is methylated
why might imprinting exist?
in general, genes that enhance embryonic growth (lgf2) are imprinted in females; genes that repress embryonic growth (H19) are imprinted in males
chromosome count
Losing or gaining an autosome is a bad thing for humans
-trisomy of all autosomes except 21 is fatal
-monosomy of all autosomes is fatal
But monosomy and trisomy of X are ok
In mammals, X inactivation is another form of epigenetics, why?
modification of the genome outside the actual DNA sequence
Barr body
represents the inactive X chromosome
X inactivation is …?
random & takes place early in development, between 4-cell and 32-cell stage
the inactivation will be maintained in all the daughter cells of each cell
is the whole X chromosome inactivated?
the entire X chromosome is not inactivated-there is a small section where transcription still takes place
-this has consequences for individuals with abnormal sex chromosome combinations
why don’t sex and gender always match?
- Mutations
- Hormones
- Chromosomal number abnormality
mutations
a person could have a translocation of the SRY gene onto an X chromosome: XX but appear male
hormones
a person could be chromosomally male or female, but have a deficit or excess of hormone production or reception
-Most common example Androgen Insensitivity Syndrome (AIS) =chromosomally XY but phenotypically female
chromosomal number abnormality
sometimes people have too many or too few sex chromosomes; this results primarily in the infertility, but can also result in ambiguous external sex characteristics depending on hormone production
what is the actual mechanism of X inactivation in mammals?
a complex on the X chromosome the XIC (X inactivation center) is responsible for X inactivation
Xist
the main gene of interest in X inactivation
the state of Xist is opposite to the rest of the X chromosome
Tsix
another gene involved (Xist backwards) it is active when Xist is inactive
When Xist promoter is ACTIVE (unmethylated)
Xist is made & that X chromosome is inactivated
When Xist promoter is INACTIVE (methylated)
Xist is not made & that X chromosome is active
The Xist gene
- does not get translated into a protein
- instead makes a long RNA that coats the X chromosome
- initiates further meythlation
Xist action
-the Xist mRNA coats the chromosome that it is transcribed from: it only acts in “cis”
Once Xist mRNA is transcribed:
-the promoters of additional genes along that X chromosome are methylated
-these methylations are preserved so that the same chromosome remains inactivated even after many rounds of cell division
poylgenic trait
traits determined by the combined effect of 2 or more pairs of alleles
single gene, complete dominance
discrete phenotypes
discrete distributions
single gene, incomplete dominance
discrete phenotypes
discrete distributions
multiple genes, incomplete dominance
continous phenotypic traits
continous (normal) distributions
additive alleles
each allele contributes EQUALLY to the trait
you can see the effect of BOTH alleles
if you know the number of phenotypic classes
use 2n+1 =# of phenotypic classes
if you know the frequency of individuals in an extreme class
(1/4)^n=frequency of extreme
heritability
proportion of total phenotypic variance due to genetic differences among individuals
phenotypic variation
variation of a trait can be separated into genetic and environmental components
Var(P) = Var(G) + Var(E) +2Cov(G,E)
genotypic variance Var(G)
variation in phenotype from differences in genotype
environmental variance Var(E)
variation in phenotype from environment
genotype-environment 2 Cov(G,E) interaction
environmental effects on phenotype differ according to genotype
heritability numbers
estimates apply only to a particular group in an particular environment–does not apply to individuals, only to variations in a group
even the most highly heritable traits can be modified by the environment
single gene trait
one gene with two or more alleles results in two distinct phenotypes
discontinous characteristcs
exhibits only a few, easily distinguished phenotypes
yes/no
polygenic trait
varying phenotypes result from input of multiple genes that contribute additively (collectively) to the phenotypes
complex trait (quantitative)
multiple genes (usually) and environment yield a continuous distribution of phenotypes
polygenic trait graphs
the greater the variance, the more spread out the distribution is about the mean
variance (sd^2)
the average squared distance of all measurement from the mean
-measure of variation within a population
why is variance important?
because many polygenic traits are also influence by the environment
heritability
the proportion of the total phenotypic variance in a population due to genetic differences among individuals
heritability estimate
expresses the likelihood of a trait being passed on from parent to sibling
-if a trait has high heritability, the offspring are more likely to express that same trait
how do you measure Var(G)?
take genetically identical seed and genetically diverse seeds and grow both in the same environment
small Var(E) –>
contribution from genetics appears larger (larger h)
large Var(E) –>
contribution from genetics appears smaller (smaller h)
Quantitative Trait Locus
a segment of DNA that affects a quantitative (continuously varying) trait
basic principles of QTL mapping
- need markers closely linked to QTLs of interest
- Need a mapping population in which each true breeding line has defined marker alleles
- Cross two inbred (pure breeding) strains to produce F1, then backcross the F1 to parental strain
what can markers be?
RFLPs, SNPs, micro satellite, etc.
Anything that can be measure on a gel
purpose of back cross?
generate offspring that have chromosomes mostly from one parent strain and only a few from the other parent stain
