Exam 2 Flashcards
Wild type allele
occurs most frequently in a population
often dominant
standard against which mutations are compared
Loss of function mutation
mutation causes diminution or loss of wild-type function
Null allele
loss of function mutation with complete loss; produces no functional gene product, usually recessive
Gain of function mutation
enhances function of wild-type product, usually by increasing its quantity
usually dominant
Drosophila allele system
allele written uppercase or lowercase depending on whether mutation is dom or recessive
wild-type alleles (nonmutant) are designated with a superscript +
Incomplete / partial dominance
crossing two parents with contrasting traits produces offspring with an intermediate phenotype
for example, red + white flowers = pink flowers
neither allele is dominant
Codominance
two alleles of a single gene are responsible for producing distinct gene products
Joint expression of both alleles in a heterozygote
both are expressed; don’t ‘blend’ like in incomplete
Molecular basis of complete dominance
the heterozygote creates a nonfunctional protein with the recessive gene, and a functional protein with a dominant gene
dominant gene product determines the trait
recessive homo doesn’t produce any functional proteins
Molecular basis of incomplete dominance
caused by “dosage” effect:
- two doses produces the greatest amount of functional protein
- one dose produces less, not fully reaching homo phenotype
- zero doses, no functional protein
i.e, products in a dom homo are sufficient to produce the phenotype, hetero are insufficient to fully reach the phenotype; in a recessive, no products
Cause of lethal alleles
represent interruptions to essential genes, such as deletion mutations
recessive lethal allele
may produce unique mutant phenotypes when heterozygous
kills when homozygous (not necessarily when homo recessive; dominant genes can be recessive for lethal; just means 2 copies are needed)
dominant lethal allele
one copy of the allele is enough to kill
much rarer because harder to pass down
usually develop later in life after offspring have been produced
Pleiotropy
single gene can have many different effects
the gene product has multiple functions, thus affecting many phenotypes
- protein may be used in several different places
- other processes may depend on protein
gene interaction
several genes influence single characteristic
does not imply interaction between products directly, rather: cellular function of gene products contribute to phenotype
Epigenesis
each step of development contributes to the final appearance
gene products may exist in a biochemical pathway dependant on the functioning of several genes
Epistasis
expression of one gene or gene pair masks or changes the expression of another gene or gene pair, due to the implications of one product on the other
Recessive epistasis
recessive genotype masks expression of another dominant gene
Dominant epistasis
dominant allele at one locus masks expression of all alleles at a second locus
Complementary gene expression
Both genes work together to produce a final product
Complementation
Two genotypes may cause the same phenotype
Thus they can produce offspring without the phenotype
Complementation Analysis
an experimental approach used to analyze the cause of a phenotype
IF NORMAL = COMPLEMENTATION
IF ABNORMAL = NO COMPLEMENTATION
[complementation] normal development
mutations are in separate genes, not alleles of each other
following cross, heterozygous for both genes; normal products of both genes are produced by normal copy of each
complementation occurs
[complementation] abnormal development
mutations affect same gene and are alleles, so no normal gene product
complementation does not occur
Complementation groups
All mutations belonging to a single gene
will complement mutations in other groups
with large numbers of complement groups studied, it is possible to predict # of genes involved in determining a trait
X-linkage
mutations attached to the x chromosome
results in unique patterns of inheritance, dependant on sex
Hemizygous
males cannot be homo/heterozygous for x-linked genes
express whatever’s on their single X
Crisscross pattern of inheritance
traits controlled by x-linkage are passed from homozygous mothers to all sons
sex-limited inheritance
A trait that is expressed in one sex, even though the trait is not X- or Y-linked
sex-influenced inheritance
phenotypic expression conditioned by the sex of the individual
Heterozygote may express one phenotype in a male and another in a female
could be dominant in one sex or recessive in the other
Degree of expression
some mutant genotypes produce individuals whose phenotypes are essentially normal; extent of mutation’s presence is measured in penetrance and expressivity
penetrance
percentage of individuals who show some degree of expression of a mutant genotype; how often the phenotype occurs in population
observed phenotype expression / expected phenotype expression (o/e)
Expressivity
range of expression of mutant genotype
i.e, eyeless gene in mutant flies; average expression is reduction of eye size, but expression ranges from complete loss of both eyes to completely normal eyes
conditional mutations
phenotypic expression is determined by environmental conditions
temperature-sensitive mutations
conditional mutation that produces a mutant phenotype at a given temperature
i.e, enzyme only active in warmer temperatures; enzyme affects phenotype
Permissive condition
the condition where the conditional mutation is shown
Restrictive conditions
conditions under which the conditional mutation does not show
Genetic anticipation
with each generation that inherits some genetic disorder, the symptoms intensify and the age of onset decreases
caused by expansion of trinucleotide repeats in or near a gene
Ratio of recessive epistasis
9:4:3
Ratio of dominant epistasis
12:3:1
Double recessive epistasis
One dominant allele at each of 2 loci is needed for wild phenotype
two genes whose combined dominant function give the dominant phenotype, but whose recessive phenotypes overrides the dominant phenotype in the other, giving a recessive phenotype.
MUTUAL MASKING
form of complementary gene action
Heterogametic sex
Unlike gametes; ZW, XY, X0
always determines sex of progeny
Male not always heterogametic
Homogametic sex
Like gametes, XX, ZZ
Klinefelter
XXY
Turner
X
Reciprocal translocation on sex chromosomes
Causes XY to develop female and XX male
SRY mutation; SRY jumps from Y to X or vice versa
Physical process of sex differentiation
- embryo hermaphroditic early in development
- bipotential gonadal ridges appear, sexually indeterminate
- gonadal ridges differentiate into testes with Y chromosome present
Bipotential gonads
Undifferentiated gonadal ridges early in development
PAR
Pseudoautosomal region of Y chromosome; shares homology with X, pairs during meiosis
Male-specific region of Y
divided equally between euchromatin and heterochromatin; doesn’t pair during meiosis
contains SRY
SRY
Sex-determining region of Y
gene region that controls male development
encodes for TDF
TDF
testis-determining factor
causes testicular formation; encoded by SRY
Primary sex ratio
ratio of sex at conception; equal amounts of female and embryos conceived; more XX die during development
Secondary sex ratio
Sex at birth; more XY than XX born
Dosage compensation
The idea that XX should have a higher ‘dosage’ of genes, leading to problems with X-linked genes
In order to balance the dose of genes, a dosage compensation mechanism inactivates all but 1 X in a cell
Barr body
an inactivated X chromosome
all but 1 X will become a Barr body
not all genes on Barr body are inactivated; Xic
Lyon hypothesis
postulated that inactivation of X occurs randomly in cells at a point early in embryonic development
not all cells have the same inactivated X
Lyonization
Random inactivation of an X chromosome
Xic
X inactivation center
major control unit of X chromosome; expressed only on inactivated X
has a gene XIST which is critical for inactivation
Imprinting
the same X chromosomes are inactive in subsequent divisions
one or both chromatin components are chemically modified, silencing them Forever
Drosophila sex determination system
The X:A ratio determines sex
more X than A = female, less X than A = male fly
2X:2A (1) is a female fly, 1X:2A (.5) is a male fly
The presence of an additional X alters the balance and results in female differentiation
Location of sex-related genes in drosophila
X chromosomes have ‘femaleness genes’
‘maleness genes’ are on autosomes
the Y chromosome in flies affects male fertility; non-Y male flies are infertile
Metafemales
many X chromosomes, such that X:A ratio exceeds 1:1
weak and sterile
Intersex drosophila
0.5 < X:A < 1.0
(between standard male and standard female)
Metamales
X:A ratio is less than 0.5, more autosomes than X
weak and sterile
Genetic basis of Drosophila sex differentiation
A cascade of regulatory gene expression converts X: A ratio into a molecular signal
3 regulatory genes, which are spliced differently between sexes
Females have regulated splice sites, whereas males do not (making males the ‘default’)
SXL
sex-lethal
the “master switch”; X-linked
expression of Sxl relies on ratio of X:A of 1
in males, sxl not activated
in females, sxl activated
X chromosomes code for promoters for SXL, whereas autosomes code for repressors; if there are more autosomes than X (as in males), SXL is repressed
TRA
transformer
if Sxl present, produces female TRA protein
if no Sxl present, no TRA protein made
this protein influences expression of dsx
dsx
doublesex
regulator of sex-related gene expression
RNA spliced differently in males and females, as told by presence of TRA product; product of splices induces different differentiation
if female TRA protein is present, will create female DSX protein
if no TRA protein is present, will create male DSX proteins (DSXM)
dsxm
male DSX proteins
represses genes required for female development, activates male specific genes
Drosophila dosage compensation
no barr bodies, completely different system
X-linked genes in males are transcribed at twice the level of comparable genes in females due to DCC
DCC
dosage compensation complex; creates gene-activating proteins
will activate male X-linked genes more often, to give an equivalent dosage
Temperature dependent sex determination
steroids affected by temperature are important in sex determination in these systems
Aromatase
converts androgens into estrogens
activity correlates with reactions in gonadal development; high in ovaries, low in testes
thermosensitive factors may mediate transcription of aromatase in TSD systems
Interplay of genetic and temp differentiation systems
animals can have XX/XY chromosomes, but during development can be converted between sexes at different temperatures
Chromosome mutations
changes in total # of chromosomes
deletion or duplication of segments of chromosomes
rearrangement of chromosomes
Aneuploidy
Organism gains or loses one or more chromosomes, but not a complete set
Better tolerated in plant kingdom
Can alter phenotype drastically; sex-chromosome aneuploidy has a less drastic effect than autosomal aneuploidy
Monosomy & Trisomy
Monosomy
Type of aneuploidy
loss of a single chromosome from an otherwise diploid genome; 2n-1
usually not tolerated for autosomes
Haploinsufficiency
a single copy of a recessive gene due to monosomy may be insufficient to provide life-sustaining function
Trisomy
gain of a single chromosome to an otherwise diploid genome 2n+1
somewhat more viable in autosomes for small chromosomes
Usually viable in plants, but with altered phenotypes
2 complications of monosomy
if just one gene on an inherited chromosome is a lethal allele, monosomy unmasks its expression in heterozygotes
haploinsufficiency also causes inviability
Euploidy
complete haploid sets (n) of chromosomes are present
individual has the correct number of chromosomes in them
Polyploidy
several extra sets of chromosomes are present (several n)
common in plants, not animals
Associated with greater cell size
Naming of polyploids based on number of chromosomal sets; triploid is 3n
Autopolyploidy & allopolyploidy
Odd-numbered polyploidy
Odd numbers of chromosome sets not usually maintained between generations
tripolyploid organisms don’t produce genetically balanced gametes, so they are sterile
Autopolyploidy
addition of one or more extra sets of chromosomes, identical to normal haploid component of same species
often sterile
new polyploids can be induced using chemicals like colchicine
autotriploids & autotetraploids
Colchicine
colchicine interferes with spindle formation, preventing migration to the poles
failure of cell division results in doubling of chromosome numbers
Autotriploids & 3 causes
3n, Autopolyploidy
failure of chromosomes to segregate during meiosis, creating diploid gamete
fertilization of single egg by two sperm, creating triploid zygote
diploid + tetraploid = triploid (n + 2n = 3n)
sterility (3 homologs can’t properly pair in meiosis)
Autotetraploids
4n, Autopolyploidy
arise by fusion of two diploid gametes
can be semifertile, as they produce balanced gametes; but their synapsis might produce univalents, trivalents, and quadrivalents, so good luck
Allopolyploidy
combination of chromosome sets from different species, as a result of hybridization
use A and B to represent haploid set of chromosomes for two unrelated species
Sterile hybrid in allopolyploidy
When the haploid gametes of 2 species fuse, a hybrid is created
for A of 2n=6 and B of 2n=4, AB has 5 chromosomes
this hybrid is sterile because there are no pairing partners
Amphidiploid
allopolyploidy
Hybrid fertility can be restored by chromosomal doubling, a result of a cellular error (induced by chemicals like colchicine).
two diploid genomes combined = fertile allotetraploid
functionally diploid, forms bivalents during meiosis because every chromosome has one homologous partner
Chromosomal breakage
Chromsomes can “break” due to exposure to chemicals or radiation
ends at the points of breaking are “sticky” and rejoin other broken ends
this results in a rearrangement of genetic information
Heterozygous for the aberration
chromosomal rearrangement is found in one homolog, but not the other
unusual pairing formations found in meiotic synapsis
Effect of being heterozygous for the aberration
if no loss of genetic information occurred, unlikely to be affected phenotypically
gametes may be duplicated or deficient for some chromosomal regions; OFFSPRING might show mutant phenotype
Duplications & deletions
total amount of genetic information in chromosome changes
Translocations & inversions
exchanges and transfers
locations of genes are altered within the genome
Ratio of double recessive epistasis
9:7
Deletion
Chromosome breaks; segment without centromere is lost
Compensation loop during meiosis; normal buckles
Duplication & 3 consequences
any part of the genome is present more than once
may result in redundancy, phenotypic variation, and multigene families
Terminal deletion
occurs near the end of chromosome
Intercalary deletion
occurs in the chromosome’s interior
Compensation loop
for synapsis between a deleted chromosome and its homolog, the normal chromosome must buckle out
for synapsis between a duplicated chromosome and its homolog, the duplicated chromosome must buckle out
Gene redundancy
The presence of several genes in an organism’s genome that all have variations of the same function
caused by duplication
Multigene families
groups of contiguous genes whose products perform the same or similar functions
come from an “ancestral” set of genes via duplication
Copy number variation
duplications of portions of genes happen regularly; the number of copies in individuals differs
CNVs are important in the expression of many traits, including diseases
Inversions
segment of chromosome is flipped
doesn’t involve loss of information, just rearranges the gene sequence
requires breaks at two points along length of chromosome, and reinsertion of inverted segment
if heterozygous, normal synapsis is not possible; inversion loop must be formed
Paracentric inversion
centromere is not part of rearranged chromosome section
Pericentric inversion
centromere is part of rearranged chromosome section
Inversion heterozygotes
only have one inverted chromosome in a pair of homologs, such that during synapsis they must form an inversion loop
Inversion loop & segregation
occurs in heterozygotes
if crossing over doesn’t occur within the inverted segment of the inversion loop, homologs segregate
if crossing over does, abnormal recombinant chromatids produced; each has some duplication and deletion; one is dicentric, the other acentric
dicentric chromatid
recombinant chromatid produced from crossing over in a paracentric inversion
two centromeres
contains duplications and deletions
dicentric chromatid behavior in meiosis
pulled in two directions, usually breaking; part of the chromatid goes in one gamete, and the rest into another
gametes containing these are deficient in genetic material
acentric chromatid
recombinant chromatid produced from crossing over in a paracentric inversion
lacking a centromere
contains duplications and deletions
moves randomly to one pole during anaphase I, or might be lost; produces inviable gamete
Evolutionary advantage of inversions
inversion heterozygotes suppress recombination among genes in the inverted region
sequence of alleles at adjacent loci are preserved
Translocation
movement of chromosomal segment to new location
no genetic information lost or gained
Reciprocal translocation
exchange of segments between non-homologous chromosomes
two nonhomologous chromosome arms exchange at break points
Heterozygous for a reciprocal translocation in meiosis
“crucifix” shaped pairing of homologs
4 chromosomes involved, including unaffected homologs, and both translocated chromosomes
produces half genetically unbalanced gametes (semisterility)
Alternate segregation
normals move to one pole, translocated to another
produce viable gametes; both possess one complete set of the chromosome segments
Adjacent segregation
for chromosomes 1 and 2, where N is normal and T is translocated
N1 and T2 move towards one pole, N2 and T1 move towards another
produce nonviable gametes containing duplications and deficiencies
Semisterility
half of the gametes from someone heterozygous for reciprocal translocation are viable
Roberstonian translocations
chromosomal breaks occur near centromeres
fragments containing centromeres rejoin
generates one large chromosome and one small acentric chromosome, which is lost
chromosome number is reduced
Familial down syndrome
long arm of 21 and short arm of 14 swap
large chromosome of two long arms, short chromosome lost
people with the translocation are called ‘carriers’; phenotypically normal, but increased chance of producing abnormal children, as their gametes may segregate in Strange Ways
Familial down syndrome gamete segregation
STYLE 1:
half of the gametes will have N21 and N14; normal offspring
half of the gametes will have T14+21; carrier
STYLE 2:
half of the gametes will have N21 and T14+21, aka 2 copies of 21 information; down syndrome
half of the gametes will have N14 and no 21; aborted
Fragile sites
unstable chromosome regions prone to breakage
one is on the X chromosome, associated with mental retardation
results from an increase in # of repeats of CGG
Incomplete Dominance notation
denoted with superscripts attached to uppercase letters
Doubling
The restoration of fertility in sterile allopolyploid plants; the chromosome number doubles such that the plant is now amphidiploid.
Cause of duplication
arise as the result of unequal crossing over during prophase I
Pericentric inversion loop crossing over
The two chromatids involved in the crossing over will contain duplications and deletions, making them inviable for gametes; but they aren’t di- or acentric
Nondisjunction
the failure of homologous chromosomes or sister chromatids to separate during cell division
creates aneuploidy
