Unit 2 Day 2 Flashcards
balanced structural aberration
- normal complement of chromosomal material, no loss or gain
- reciprocal translocations
- roberstonian translocations
- inversions
unbalanced structural aberration
- abnormal chromosome content
- deletions
- duplications
- isochromes (duplications short/long arm)
- marker (ring) chromosomes
- recombinant chromosomes
Structural rearrangements require what type of breaks?
double strand breaks
results deletion, inversion, reciprocal relocation
occur in repeat sequences in homo/non-homo chromosomes
reciprocal, interchromosomal exchange (translocation)
break in arm of each of 2 chromosomes
reciprocal exchange of segments
balanced (apparent) translocations
no loss or gain of genetic material
no phenotypic effect for heterozygote
exception: breakpoint in a gene disrupting function
quadrivalent formation
meiosis 1
reciprocal translocation
normal and translocated arrange to maximize sequence pairing at zytotene
form quadrivalent
segregation described by relationship of the centromeres to each other
alternate segregation
centromeres of homologues go to opposite poles
leads to gametes with normal chromosomes
gametes with both derivatives (balanced)
only mode of segregation leading to gamete with full complement of chromosomes
adjacent 1 segregation
abnormal segregation
adjacent centromeres go to same pole
nonhomologous centromeres
most common when translocated segments are small
results in trisomy and monosomy for translocated segments
balanced translocation carriers
risk of unbalanced progeny (risk=0-30%)
maternal carriers-more likelihood of offspring with phenotype
robertsonian translocations
structural chromosome rearrangement
centric fusion
joining of two afrocentric chromosomes at the centromere, short arm (satellite, repetitive sequences, no euchromatin, no protein coding, no effect)
balanced!!!!!
phenotype of robertsonian translocations
most common structural chromosome rearrangement
usually no phenotype (no loss euchromatin)
risk to have offspring with unbalanced karyotype
prevalence infertile men
most common robertsonian translocations
13;14=75% of all RTs (one of most common in humans)
14;21
21;21
all can be de novo and familial
de novo unbalanced robersonian translocations
46 chromosomes
normal homologue+RT “homologue” (leads to trisomy 21)
RT involving 13 and 21 can lead to viable trisomies
Trisomy 13 from Robersonian
20% of trisomy 13 is derived from translocation
familial and de novo (mostly de novo)
intrachromosomal rearrangement
inversion balanced (most cases) normal phenotype (carrier, most cases) familial-more common up to 1% of pop
pericentric inversions
inverted segment includes centromere
breaks in p and q arms
orient by rotating inverted segment, old fast the flanking segments of chromosome
benign pericentric inversions
heteromorphic variants
inversions containing constitutive heterochromatin (***9qh, 16qh, 1qh, Yqh)
pericentric, g-positive bands of 19p12 or q12
almost always familial
not associated with increased SABs, infertility, or recombinant offspring
inversions during meiosis
pericentric inversions form loop (during homologous pairing of meiosis)
issue-how to get maximal pairing
potential for recombinant chromosomes
outcomes of recombination in pericentric
- one recombination event is predicted within the inverted segment of the inversion chromosome and homolog in chromosome
- crossover btw. 2 non-sister chromatids=2 complimentary recombinants
- duplication of long arm, deletion short arm flanking segments (vice versa)
metotic recomb in inversion carriers
- possible gametes: normal unrearranged; inversion, balanced (these 2 are 50%)
- two complementary recombinants (one loveborn, one lethal)
rec 8
term infant appropriate size hispanic descent alamosa VSD hypertelorism, thin upper lip wide face
inversion 8 carriers
recurrence risk 6.7%
paracentric inversions
inversion segment excludes centromere 2 breaks w/in same chromosome arm difficult to detect familial and sporadic turner syndrome variant, Xp/q inversions
chromosome 22 rearrangements
mediated by segmental duplications
deletion or duplication can result in same phenotype
epigenetics
mitotically and meiotically heritable variations of gene expression that are not caused by changes in DNA sequences.
examples of epigenetic mechanisms
alter chromatin structure, affect gene expression
reversible, post-translational modifications of histones and DNA methylation
genetic imprinting
sex-dependent epigenetic modulation of regulatory regions such as promoter sequences
paternally/maternally imprinted
DNA methylation as mediator of genetic imprinting
marks are established in gamete
stably maintained in somatic cells after fertilization
reversible
reset during gametogenesis to transmit appropriate sex-specific imprint to progeny
where does somatic maintenance of imprinted regions occur?
in somatic cells
epigenetic memory
establish new epigenetic markers based on if sperm or oocyte
gametogenesis in absence of erasure and resetting
embryos with no active copies, or two active copies, of imprinted genes would be produced at high frequencies
imbalance in gene expression/imprinting
how are deletions caused?
- result from repeat misalignments
- in PWS/AS they result from presence of low copy repeats in vicinity of the common breakpoints in patients, derived from large genomic duplications of gene HERC2.
what can prader willi result from?
uniparental disomy
2 maternal imprinted chromosomes since had nondisjunction event and male gamete was kicked out.
