Chromosome Abnormalities I, II and III Flashcards
In meiosis, after DNA replication, cells undergo ___________
Two successive rounds of chromosome segregation
In meioses, chromosome content is reduced from __________ in the first meiotic division and from __________ in the second meiotic division.
4n to 2n and 2n to n
Reciprocal recombination events occur during __________
Prophase I
On average, ______ crossovers occur on each chromosome.
2-3
A genetic consequence of meiosis is reduction is chromosome number from _________ to _________
Diploid to haploid
Meioses II is much like __________
A mitotic divisions
Reciprocal recombination events between maternal and paternal sister chromatids generate ___________
Chiasmata
What is a metacentric chromosome?
The centromeres is located in the middle of the chromosome such that the two chromosome arms are approximately equal in length.
What is a submetacentric chromosome?
The centromeres is slightly removed from the center.
What is a acrocentric chromosome?
The centromere is near one end of the chromosome.
In the two hit theory, the first hit is _____________, caused either by a lack of chasm or their mislocalizations, resulting in a chromosome more susceptible to possible nondisjunction.
Diminished Recombination
The second hit of the two hit theory is the ability of oocytes to successfully ____________ in the presence of unfavorable recombination events is through to diminish over time
complete chromosome segregation
A second model suggests that the degradation of ________ over the course of the extended meiosis I arrest in oocytes results in the precocious separation of homologs
Cohesin
The age related degradation of cohesion established during detail development has been postulated to allow ____________
The movement of the chiasmata towards the ends of the homologs
Characteristics of Trisomy 18: Edward’s Syndrome.
Mental retardation and hand clenching
Characteristics of Trisomy 13: Patau syndrome
Facial clefts, hand clenching, mental retardation
Characteristics of 47, XXY: Klinefelter syndrome
Tall stature, hypogonadism, sterility, language impairment
Characteristics of 45, X-Turner Syndrome
Short stature, webbed neck, edema of hands and feet, broad, shield like test, narrow hips, failure of ovarian maintenance.
When does germ line mosaicism occurs?
Exists when a somatic mutation occurs early in development and generates mutant sub-population of germ cells.
Most children with Down Syndrome have 47 chromosomes, the extra member being a small ___________
Acrocentric chromosome
The meiotic error responsible for trisomy 21, usually occurs during maternal meioses, predominantly in _________, but about 10% of cases occur in paternal meioses, usually __________
Meioses I and Meiosis II
Chromosomal rearrangement require two ___________ and can be induced by a variety of DNA damaging agents
DNA double strand breaks
Structural rearrangements can be __________ and can also lead to further rearrangement during meiosis.
inherited
What are balanced structural rearrangements?
Normal complements of chromosomal material with no loss of genetic material
What is an inversion?
A balanced structural rearrangement and occurs when one chromosome undergoes two double strand breaks of the DNA backbone and the intervening sequence is inverted prior to the rejoining of the broken ends
Paracentric inversions _________ the centromere
Exclude
Pericentric inversions ___________ the centromere
include
What is a reciprocal translocation?
Results from the breakage and rejoining of non-homologous chromosomes, with a reciprocal exchange of the broken segments
Carriers of reciprocal translocations have increased risk of producing ___________
Unbalanced gametes
When the chromosomes of a carrier of a balanced reciprocal translocation pair at meiosis, a ___________ is formed.
Quadravalent
The quadravalent structure formed by reciprocal translocation can lead to three segregations. What are they?
- Alternate 2. Adjacent 1 (leads to unbalanced gametes) 3. Adjacent 2 (lead to unbalanced gametes)
What is a robertsonian translocation?
The fusion of two acrocentric chromosomes within their centromeric regions, resulting in the loss of both short arms
What is an unbalanced deletion?
Loss of genetic information that can arise from simple chromosome breakage and rejoining, unequal crossing over between misaligned homologous chromosomes or sister chromatids or by abnormal segregation or a balanced translocation or inversion
A deletion can be ________ or ___________
terminal, interstitial
__________ is generally less harmful than an unbalanced deletion.
Unbalanced duplication
What is an isocrhomosome?
A chromosome in which one arm is missing and the other is duplicated in a mirror image fashion, possibly occurring through an exchange involving one arm of a chromosome and its homolog at the proximal edge of the arm, adjacent to the centromere.
A small percentage of ___________ patients have 21q21q isochromosome
Down’s Syndrome
What is DiGeorge syndrome?
Example of contiguous gene syndrome, which is an abnormal phenotype caused by over-expression or loss of neighboring genes. Causes serious heart defect. Caused by a deletion on chromosome 22.
What is Velocardiofacial syndrome?
Example of contiguous gene syndrome, which is an abnormal phenotype caused by over-expression or loss of neighboring genes. Causes cleft palate and septal defects. Caused by a deletion on chromosome 22.
To be completely stable, a rearranged chromosome much have _________ and __________
Functional centromere and two telomeres
A ring chromosome is likely to be formed when a chromosome undergoes ____________ and reunite
Two breaks
The molecular basis of imprinting is based on __________
The allele-specific methylation of CpG dinucleotides in the promoter regions
Hypermethylation in gene silencing, may directly inhibit transcription by ____________ or _________
Repelling transcription factors or actively recruit factors that repress transcription.
What are the three characteristics of imprinted genes?
- These genes tend to be clustered together rather then spread throughout the entire genome 2. These clusters contain both maternally and paternally imprinted genes. 3. The imprinted genes encode both proteins and non-coding RNA’s
DNA demethylation reactivates gene expression and erases the parental methylation pattern in developing gametes. Demethylation could result from the _____________ or indirectly through ___________
inhibition of the maintenance methyltransferase; inactivation of chromatin-remodeling proteins
Erasure and resetting of the imprint appear to occur at imprinting centers, which contain non-coding DNA sequences that bind impinged RNA transcriptions, called ___________ and recruit DNA methyltransferase complex that methylate CpG islands located near the IC on the same chromosome (cis).
BD transcripts.
In 70% of Prader Willi cases, the syndrome is the result of a deletion invoking the long arm of chromosome _________ occurring on the homolog inherited from the _________
15; father
Angelmen’s syndrome has a same deletion on chromosome _____________ but on the __________ homolog
15; maternally-derived
_____________ commonly occurs when a trisomic conceptus loses one of its extra chromosomes due to mitotic nondisjunction in early gestation
Uniparental disomy
A young child present to you office with a genotype 46XY del (15) (q11q13) on the maternal chromosome. Which of the following clinical features would be most consistent with the patient’s genotype?
Seizures - if the is child has a material deletion of chromosome 15, that have Angelman’s Syndrome,
In adjacent 1 segregation, homologous centromeres go to __________
different daughter cells
In adjacent 2 segregation, both homologs go to __________
The same daughter cell
Paternally and maternally derived homologous chromosomes synapses along their entire length to form bivalent structure during which phase of meiosis?
Prophase I
Paternal error in _________ results in 47XXY Klinesfelter’s.
Meiosis I
46 X i(Xd) indicates __________
Female with isochromosome for the long arm of X
What is the genotype of a male with fragile X?
46, Y fra(x) (q27.3)
What percentage of offspring from an individual whose genotype is i21 will be abnormal?
100%; i21 is the isochromosome for 21 meaning that the long arms of 21 has fused and it is impossible for the gamete to be haploid. 50% of the gametes will not receive a 21 and the other 50% will get the isochromosome and be trisomic for 21
