Genetics 2 Flashcards
Midterm 2
Recombination:
production of new allele combinations
Independent assortment of genes at meiosis
interchromosomal recombination
major means by which organisms produce new combinations of allels
Recombinant:
Any meiotic product that has a new combination of the alleles provided by the
two input genotypes
Meiotic recombination:
is any meiotic process that generates a haploid product with new
combinations of the alleles carried by the haploid genotypes that united to form the meiocyte
Haploids (single set of chromosome in each cell)
Recombinants are meiotic output different from meiotic input.
This is because meiotic input is the genotype of individuals (haploid since meiosis) and and the meiotic output is the two parental inputs (meiotic input) along with the recombinants
e.g., AB + ab (inputs)
meiotic diploid = AaBb
output (from crossing with itself) = AB, ab, aB, Ab
Diploids (2 sets of chromosomes in each cell)
recombinants
are best detected in a testcross
Input and output are gametes (reproductive cells)
-To know input gametes: pure breeding parents
e.g., AABB + aabb
INPUTS = AB + ab
-To detect recombinant output gametes:
testcross and observe progeny
meiotic diploid = AaBb
cross with test cross (aabb)
output are the F2 and will include the parental genotypes with the recombinants
Recombinant frequency (RF):
The proportion (or percentage) of recombinant cells or individuals
- A recombination frequency of 50% indicates
that the genes are independently assorting
and are most likely on different chromosomes
Diagnostics of Linkage
-When two genes are close together on the same chromosome pair (that is, when they are
Linked), they do not assort independently but produce a recombinant frequency of less than 50 Percent.
Hence, a recombinant frequency of less than 50 percent is a diagnostic for linkage
Two types of meiotic recombination
Interchromosomal recombination:
Recombination by Mendelian independent assortment (RF = 50%)
● Intrachromosomal recombination:
Crossing over (RF < 50%)
- Homologous recombination – molecular mechanism of crossing ove
Homologous recombination – molecular mechanism
of crossing over
-For linked genes, recombinants are produced by crossovers between nonsister chromatids during meiosis
-When homologous chromosomes pair at
meiosis, the chromosomes occasionally
break and exchange parts in a process
called crossing over.
- A cross-shaped
structure called a chiasma (pl., chiasmata)
often forms between two nonsister
chromatids.
Chromosome map:
shows unidirectional arrangement of genes on a chromosome
Gene Position on a chromosome known as locus
-2 types of maps:
● Recombination-based maps: map of genes identified by mutant phenotype showing single gene inheritance. Recombination maps are generated with linkage analysis
● Physical Maps: genes as segments along DNA of chromosome
Three-point testcross
● cross of a trihybrid (triple heterozygote) with a triply recessive tester
● deduce whether three genes are linked, if so deduce their order and distances between them
Linkage Symbolism and Terminology
-cis = AB/ab or ++/ab (dominant alleles on the same homolog)
-trans = dominant alleles on opposite homolog Ab/aB or
- alleles are always written in the same order on each homolog
-slash separates the two homologs for linked alleles
-semi colon separates the two homologs for unlinked alleles A/a;B/b
-period separates two homologs for alleles with unknown linkage A/a . B/b
Heteroduplex DNA
-DNA THAT CONTAINS TWO COMPLIMENTARY strands of dna that originated front different homologs
Using ratios as diagnostics
(come back)
iNTERFERENCE
I = 1 - coc
c.o.c = observed number of double recombinants/expected number of double recombinants
observed = total number of double recombinants (sum)
expected = percentage of each double recombinant multiplied together and then multiplied with the total progeny
I = 0 : no interference between two crosses (crossovers occur independently)
If I = 1, then interference is complete. No double crossovers occur.
Allelic series
Known mutant alleles of a gene and its WT allele
Full, or complete dominance:
when the homozygous dominant cannot be distinguished from the
heterozygote at the phenotypic level.
-Fully dominant allele is expressed when only one copy is present (as in a heterozygote),
whereas the other allele is fully recessive
-
Functional Effects of Mutation
- Loss-of-function: alleles that result in a significant decrease (hypomorphic/leaky mutation) or in the
complete loss (amorphic/null mutation) of the functional activity of a gene product. - Gain-of-function: alleles that have acquired a new function (neomorphic mutation) or have their expression altered in a way that gives them substantially more activity than the wild-type allele (hypermorphic mutation)
Any heterozygote containing the new allele along with the original wild type allele will express the new allele. Genetically this will define the mutation as a dominant.
Recessive mutations are usually loss-of-function mutations (haplosufficiency).
Dominant mutations can be gain-of-function, dominant negative, or loss-of-function (in the case of haploinsufficiency).
iNCOMPLETE dOMINANCE
- First, Cross: 2 pure breeding lines
P: A/A (WT, red) x a/a (mutant, white petals)
F1 = The phenotype of a heterozygote is intermediate between those of the two homozygotes, on some quantitative scale of measurement = PINK
- sELF THE F1
1:2:1 (2 A alleles = red, 1 A allele = pink, 0 A allele = white)
Codominance
-both phenotypes expressed with equal dominance
e.g., blood groups
IA and IB alleles together express AB sugar and they are dominant to i (i alone doesn’t exress anything and paired with one of them, it is recessive)
i = null allele since ii = no A or B and gives O
IA IA = A
IA i = A
IB IB = B
IB i = B
Recessive lethal alleles
- allele capable of causing death of an organism
AY allele: yellow coat color
A allele: WT, brown (Agouti)
Cross1: AY/A (yellow) x A/A (WT)
F1 = 1 : 1 ratio AY/A (yellow) : A/A (WT)
- self them
AY/A (yellow) x AY/A (yellow)
Viable F2 = 2:1
2/3 AY/A (yellow)
1/3 A/A (WT)
Because …
¼ A/A WT
½ AY/A yellow
¼ AY/AY lethal
AY/AY = lethal in homozygous state
Pleiotropic:
allele that affects more than one property of an organism
e.g., lethal alleles since they effect viability and fur colour
Type of Lethal alleles
Recessive lethal:
- mutant allele causes death when homozygous.
-can code for dominant or recessive traits in the heterozygous state
Dominant lethal:
one copy of the mutant allele results in death
-Rarely observed; inherited and
present in the population only if lethality happens later in life
Conditional lethal:’
-viable in one environment and lethal in another
Variability in Phenotypes
Penetrance: percentage of individuals with a given allele who exhibit the phenotype
associated with that allele.
Expressivity: degree to which a given allele is expressed at the phenotypic level; i.e. intensity
of phenotype
complementation test
for diploids to test if two mutants with same phenotype are allelic or whether the mutations are in different genes:
1) cross 2 individuals homozygous for different recessive mutations
2) If progeny shows the wild-type phenotype, the two recessive mutations must be in different
genes because the respective WT alleles provide WT function, i.e. in this case we say the
mutations have complemented each other
3) If progeny does not have wild-type phenotype but shows the mutant phenotype(s) then they
do not complement and the initial recessive mutations must be allelic, i.e. different mutants
of same gene.
Complementation:
the production of a wild-type phenotype when two haploid genomes bearing
different recessive mutations are united in the same cell.
Inferring gene interactions
- Complementation Test
-If mutants are in different genes,combine the different mutants in pairs to form double mutants:
-Double mutant is obtained by crossing two homozygous recessive single mutants and selfing the F1
-Assess F2 for 9:3:3:1 which gives different types of gene interactions
Types of gene interactions
-9:3:3:1 = no gene interaction
9 a+/-;b+/-
3: a+/-;b/b
3 a/a;b+/-
1 o/o;b/b
-9:3:3:1 -> 9(WT):7(mutant) = complementary gene action
(The wild-type action from both genes is required to produce the wild-
type phenotype. Mutation of one or both genes produces a mutant phenotype)
-9:3:3:1 -> 15(wt):1(mutant) = duplicate gene action
(allows dominant alleles of either duplicate gene to produce the wild-type phenotype. Only organisms with homozygous mutations of both genes have a mutant phenotype e.g., pprr since dominant is P and R)
-9:3:3:1 -> 9:6:1 = dominant gene interaction
(occurs between genes that each contribute to a phenotype, producing one phenotype if dominant alleles are present at each gene, a second phenotype if recessive alleles are homozygous for either gene, and a third phenotype if recessive homozygosity occurs at both genes)
Epistasis
when a mutant allele of one gene masks the expression of a mutant
allele of another gene and expresses its own phenotype instead.
recessive epistasis
Recessive epistasis occurs when recessive alleles at one gene (gene 2) mask
or reduce the expression of alleles at the interacting locus (gene 1)
-9:3:4
dominant epistasis
a dominant allele
of one gene masks or reduces the
expression of alleles of a second gene
-9:3:3:1 -> 12:3:1
Suppressors
Suppressor: mutant allele of a gene that reverses the effect of a mutation of another gene, resulting in wild-type or almost wild-type phenotype
Revertant: reversal of the original mutation that results in WT phenotype
recessive suppressor that
has no phenotype
13:3
Synthetic lethals
Two mutations that are individually benign can become lethal when united in the same genotype.
F2 = 9:3:3
-double mutant = 1 and is absent
Transposable Elements (transposons)
- Genetic loci that can move from one location in the genome to another.
Transposition
A process by which mobile genetic elements move from one location in
the genome to another.
Back cross
crossing of hybrid with parent
Activator (Ac) and Dissociation (Ds
- Transposable elements in maize can inactivate a gene in which they reside, cause chromosome breaks, and transpose to new locations within the genome.
- Autonomous elements can perform these functions unaided;
- nonautonomous elements can transpose only with the help of an autonomous
element elsewhere in the genome.
Transposase:
An enzyme encoded by transposable elements that undergo conservative
transposition.
Nonautonomous transposable element
- A transposable element that relies on the protein products of
autonomous elements for its mobility. - Dissociation (Ds) is an example of a nonautonomous
transposable element.
Autonomous transposable element:
- A transposable element that encodes the protein(s)—for example, transposase or reverse transcriptase—necessary for its transposition and for the
transposition of nonautonomous elements in the same family. - Ac is an example of an autonomous
transposable element.
Insertion Sequence (IS) Element
A mobile piece of bacterial DNA (several hundred nucleotide pairs in length) capable of inactivating a gene into which it inserts.
-IS elements have inverted repeat sequences (IR) which are identical sequences but inverted
-Structure of IS elements = transposase gene with Inverted repeats on each end
Composite transposon
A type of bacterial transposable element containing a variety of genes that
reside between two nearly identical insertion-sequence (IS) elements
Simple transposons:
A type of bacterial transposable element containing a variety of genes that
reside between short inverted repeat sequences
two stages of transposition
excision (leaving) from the original location, and insertion into the new location.
Replicative transposition (“copy and paste”)
- Replicative transposition: A mechanism of transposition that generates a new
insertion element integrated elsewhere in the genome while leaving the original element at its original site of insertion. - Cointegrate: The product of the fusion of two circular elements to form a single, larger circle in replicative transposition
Conservative transposition (“cut and paste”
Conservative transposition: A mechanism of transposition that moves a mobile element to a new location in the genome as it removes that element from its previous location
Target-site duplication:
A short direct-repeat
DNA sequence (typically from 2 to 10 bp
in length) adjacent to the ends of a
transposable element that was generated during the element’s integration into the host chromosome.
Transposable elements in eukaryotes
● Class 1 transposable elements: retrotransposons
● Class 2 transposable elements: DNA transposons
Retrotransposons (come back)
A transposable element
that uses reverse transcriptase to transpose through an RNA intermediate
Aberrant Euploid
when a cell has more or less than the
normal number of chromosome sets
Aneuploid
organism gains or loses one or more chromosomes, but not a complete set (“not euploid”). The chromosome number of aneuploids is not an exact multiple of the haploid number, n
Aberrant euploidy
-Monoploids: individual of a normally diploid species that has one chromosome set
-In most species monoploids are not viable. They carry a number of recessive lethal alleles. The total set of deleterious alleles is called a genetic load. The deleterious alleles are masked by the WT
alleles in the diploid condition, but would be expressed as a monoploid
-Monoploid individuals cannot undergo meiosis successfully because the single chromosome set has no pairing partners for meiosis I. Monoploids are sterile
Polyploids
Very common in plants, rare in animals. Often associated with origin of new species.
In aberrant euploids: there is often a positive correlation between the number of copies of a chromosome set and the size and vigor of an organism (i.e. polyploids are often larger and have
larger component parts than their diploid relatives).
Higher ploidy produces larger size (e.g., 8n = large vs 2n = small)
Triploids (3n)
-2n +n
-2n + 4n
-Typically seen in plants, not animals
-pairings = trivalent (pair plus one) or univalent (unpaired homolog) plus a bivalent (paired homolog)
-Polyploids with odd numbers of chromosome sets, such as triploids, are sterile or highly infertile
because their gametes and thus their offspring are aneuploid (usually becomes inviable)
Reciprocal translocations
Genetic consequences of reciprocal translocations:
● semi sterility
● pseudolinkage of genes known to be on different chromosomes
● alterations in chromosome size
Types of Polyploids
- Autopolyploidy (auto = self): multiple chromosome sets from same species. The differentchromosome sets would be fully homologous since they originated from the same species.
- Allopolyploidy (allo = different): chromosome sets from two different but very closely related species. The different chromosomes sets in the polyploid species would be homeologous (partly
homologous)
Inversions
The main diagnostic features of heterozygous inversions are:
● inversion loops
● reduced recombinant frequency
● reduced fertility because of nonviable gametes
Balanced rearrangements
- A change in the chromosomal gene order that does not remove or duplicate any DNA.
- The two classes of balanced rearrangements are inversions and reciprocal translocations
Deletions
- Deletion of a segment on one homolog sometimes unmasks recessive alleles present on the other homolog leading to their unexpected expression.
- Pseudodominance: the appearance of a recessive phenotype due to the deletion of masking
dominant allele(s)
Nondisjunction
- a failure of normal segregation of
homologs to opposite poles at meiotic or mitotic division - Crossovers are needed to keep bivalents paired until anaphase I. If crossing over fails, first-division nondisjunction occurs.
Aneuploidy in humans
Trisomy (2n+1)
(n + 1) gamete + n gamete = 2n +1 zygote (trisomic)
Trisomics contain an extra copy of one chromosome.
In diploids, frequently results in abnormality or death, autosomal trisomies are mostly lethal in animals
Trisomy XXY (Klinefelter syndrome)
Phenotypic males.
Sterility as a consequence of altered development.
Trisomy XYY
Fertile male: X pairs with only one Y.
Other Y does not pair at meiosis I and is not transmitted to gametes (i.e. X or Y gametes, not XY or YY)**.
Trisomy XXX (Triple X Syndrome)
Phenotypically normal, fertile female.
At meiosis only two X pair, third X does not pair and is not transmitted to gametes (i.e. X gametes, not XX)**.
