Mutations/Chromosomal abnormalities Flashcards
Male pt shows high forehead, large ears, long face and prominent jaw. Pt additionally has learning disabilities. Further physical exam shows large testes, conn. tissue weakness and mitral valve prolapse
Fragile X syndrome
Triplet repeat expansion in the X chromosome
Fragile X syndrome
47 XXY
Klinefelter syndrome
Although females have another X to compensate for X link recessive disorders, which condition still can have features show in the female?
Fragile X syndrome
Female carrier can show the characteristic facial features which include high forehead, large ear, long face and prominent jaw
Pt presents with mild learning disability, reduce IQ, and exhibits self obsessed behavior. What karotype do you expect?
47 XXY
Pt with reduced IQ and gynecomastia. How would you treat?
pt is XXY
treat with testosterone starting in puberty
Conditions seen more commonly with increasing maternal age?
Klinefelter syndrome
Down syndrome
You notice short arms on chromosomes are lost in FISH test. whats going on?
Robertsonian translocation
Acrocentric chromosome
centrosome is on the end
Two acrocentric chromosomes combine and lose their satellite arms. what happens to those arms in Robertsonian translocation?
those arms contains redundant rRNA, no harm there
usually considered functionally balanced since no genetic information is lost
When can issues arise with Robertsonian translocations?
Issues can arise during chromosome segregation in meiosis I
With pachytene quadrivalents, how many outcomes can there be?
6 possible normal, balanced or unbalanced 1 normal 1 carrier 4 unbalanced
what are the two situations that result in Down syndrome
Robertsonian Translocation to 14/21 and 21
or Trisomy 21 from non disjunction in maternal meiosis I
You deliver a baby and it sounds like a cat!!! Whats wrong with his chromosomes?
deletion in terminal portion of chromosome 5
Duchenne muscular dystrophy
microdeletion on X chromosome (Xp21)
How do unbalanced insertions occur?
if material has moved within the same chromosome complement then one has a duplication and other is now missing that region
so technically, its an insertion and deletion
pericenteric inversion
involves the centromere
genes flip around the centromere
paracenteric inversions
gene swap happens in the arms
2 or more genetically distinct cell lines derived from more than one zygote
Mixoplody - chimerism
2 or more cell lines that differ in genetic constitution that are derived from a single zygote
Mixoploidy - Mosaicism
accounts for 1-2% of Down syndrome
how frequent are chromosomal abnormalities in mature oocytes?
25%
____ of all spermatozoa contain chromosomal abnormalities
10%
Meiosis definition
process of nuclear division marking the final stage of gamete formation
how does meiosis differ from mitosis?
mitosis results in 2 daughter cells, each diploid
meiosis halves the number creating 4 haploid gametes
meiosis only in the final stages of gamete formation
occurs in 2 distinct cell division events (I and II)
Meiosis I starts with and ends with?
starts with diploid cell with replicated and condensed chromosomes (XX)
ends with haploid cells with pairs of sister chromatids (X) and (X)
Meiosis II starts with and ends with?
starts with haploid cells with pairs of sister chromatids (X) and (X)
ends with four haploid cells with individual chromosomes ( I ) ( I ) ( I ) ( I )
homologous recombination
also called Cross-over
allows genetic variation in resulting offspring
what must occur for homologous recombination to occur?
chromosomes must synapse to form a bivalent (pair) for meiotic recombination to occur
errors in this process are a frequent cause of chromosomal abnormalities - translocations and inversions
Example numerical of chromosomal abnormality
Aneuploidy
which is loss or gain of one or more chromosomes
Polyploidy - addition of one or more complete haploid complements
Monosomy - loss of a chromosome
What is an example of a structural chromosome abnormality?
these are rearrangements resulting from chromosome breakage and subsequent reunion in different configuration
includes translocations, inversions, deletions, and insertions
Trisomy 21 most frequently occurs from
non disjunction in the maternal meiosis I
Non disjunction in Meiosis I results in
two disomic gametes and two nullisomic gametes
Non disjunction in Meiosis II results in
1 Disomic gamete
1 Nullisomic gamete
2 normal monosomic gametes
XXX is an example of ? and what the are symptoms?
polyploidy
no overt symptoms but there is a mild reductio in IQ and oppositional behavior
due to maternal non disjunct in meiosis I
what would you suspect of a patient showing a reduction in IQ and emotional immaturity with FISH karotype showing chromosome evident of a paternal non disjunction in meiosis II
XYY male
YY never split during gamete formation
Pt shows neck webbing and puffy extremities. You notice short stature for her age and normal intelligence but unusual social skills. What symptoms would you expect her to have later in life?
She is XO, has turner syndrome
she would have ovarian failure and narrowing of the aorta later in life
Does the inheritance of the X in Turner syndrome make any difference to the offspring?
yes, paternal X Turner pts show higher social cognition skills
45 X
Turner syndrome
In reciprocal translocations, when do issues usually arise?
during chromosomal segregation in meiosis I
If fragments exchanged in reciporal translocation are relatively equal then
there are generally no deleterious effects in the CARRIER
Reciprocal translocation
breakage of at least 2 chromosomes and exchange of fragments
Reciprocal translocations in Meiosis I
cannot form bivalents due to translocation forming a pachytene quadrivalent where each chromosome aligns with homologous material
Pachytene Quadrivalents
pattern of segregation determines is the haploid is normal, balanced or unbalanced.
Normal (1/6)
Balanced (1/6)
Unbalanced (4/6)
Microdeletion on chromosome 15 (15q11-13) results in
Prader Willi syndrome or Angleman
Angelman Syndrome
deletion on maternal chromosome 15
Prader Willi syndrome
deletion of paternal chromosome 15
You deliver a floppy baby who wont eat. Years later, mother brings in an overweight toddler showing learning disabilities. What could be the condition?
Angelman or Prader Willi syndrome
What is Prader willi/ Angelman an example of?
Imprinting - this is where the gene/region shows different expression depending on parent of origin
this is believed to be due to differences of methylation of DNA
Angelman syndrome characterized by
inappropriate laughter, ataxia and severe learning disabilities
