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Flashcards in Chromosomes Deck (25):

Basic features of a chromosome

One centromere
Two telomeres
>=1 replication origin


Types of chromosomes (by shape)

Telocentric (not human)
Acrocentric (chr 13, 14, 15, 21, 22)


Types of chromatin

1. Heterochromatin
--> Constitutive heterochromatin
--> Faculative heterochromatin
2. Euchromatin


Constitutive heterochromatin

Repetitive DNA. Different for each chromosome (can use for FISH)
Found in: Centromere, C-band positive, Satellite DNA (stalks)


Facultative heterochromatin

involved in regulation of genetic activity
More heavily methylated than active genes
X inactivation, cell type specificity,



less condensed during interphase. active


Major chromosome abnormalities found in:

8% of all conceptuses
50% of all SABs
0.7% of all live births
Most cancer cells


Position effects

Two genes put next to each other through translocation that alter the regulation of one or both with deleterious effects
(i.e. Philadelphia chromosome)


Major indications for chromosome studies

1. Child w/multiple congenital anomalies, dysmorphic features, intellectual disability, and/or developmental delay
2. Individual w/known chromosomal syndrome
3. Couple w/>=2 unexplained 1st trimester SABs or unexplained infertility
4. AMA
5. Individual w/hematologic disorder (pancytopenia, preleukemia, leukemia)
6. Individual w/neoplastic disorder assoc w/known chromosomal abnormality ( i.e. Burkitt lymphoma, Ewing sarcoma)


Trisomy 21 recurrence risk (Robertsonian translocation)

14;21: 10% if maternal, 2-3% if paternal
21;21: 100%


Function of centromere

1. provide site of attachment for spindle
2. hold 2 chromatids together during metaphase
3. site of motor responsible for chromosome movement at anaphase



Chromosomes don't segregate properly.
Can occur during mitosis, 1st meiotic division, or 2nd meiotic division.
Almost all non-disjunction is Maternal meiosis I



abnormal number of whole sets of chromosomes
(haploidy, triploidy, tetraploidy)


Uniparental disomy

Both copies of one chromosome from same parent. Isodisomy (both chr are identical) or heterodisomy (both chr are different)
Concern for imprinting effects or recessive conditions.
Caused by:
1. fertilization of nullisomic gamete by disomic gamete
2. mitotic non-disjunction in monosomic zygote
3. loss of chromosome in trisomic zygote



Abnormal number of individual chromosomes, not whole sets (monosomy, trisomy)


Meiotic segregation of reciprocal translocation

Form tetrads: one of each normal (N1, N2) and one of each translocation (T1, T2).
1. Alternate segregation: T1 and T2 go to one pole, N1 and N2 go to the other pole. All are balanced.
2. Adjacent-1 segregation: homologous centromeres disjoin. T1 and N2 go to one pole, T2 and N1 go to the other. All unbalanced.
3. Adjacent-2 segregation: homologous centromeres segregate together. T1 and N1 go to one pole, T2 and N2 go to the other. All unbalanced.
4. 3:1 segregation: 3 chromosomes go to one pole while 1 chromosome goes to opposite pole.


Reciprocal translocation

Balanced in parent. Can be balanced or unbalanced in offspring.
Overall risk for unbalanced karyotype at amnio for reciprocal translocation: 12% (i think they quote 25% at CHP?).
1/3-1/2 of unbalanced probands inherit from carrier parent.


Meiotic segregation for robertsonian translocation

Form triads: N1, N2, T1/2
1. Alternate segregation: T1/2 goes to one pole, N1 and N2 go to the other. All balanced.
2. Adjacent-1 segregation: N1 goes to one pole and N2, T1/2 goes to the opposite. Unbalanced.
3. Adjacent-2 segregation: N2 goes to one pole and N1, T1/2 goes to the opposite. Unbalanced.


Sister Chromatid Exchanges (SCEs)

Exchange of DNA between sister chromatids at homologous sites.
SCEs at repeats can result in amplification, deletion or duplication.
Increase in SCEs indicate environmental mutagens.
Increased by 10-12x in Bloom syndrome


Prader Willi syndrome (cause)

Imprinting disorder of Chr 15q12. (need paternal chr).
50% due to microdeletion of paternal 15q12, 50% due to uniparental disomy of maternal 15.
Maternal methylation of SNRPN blocks expression of ~20 other genes.


X inactivation

aka Lyon hypothesis: 1 X chr is inactivated early in random and fixed manner. Xq13.2
X inactivation center (XIC): counting mechanism that initiates XIST
X Inactive Sequence Transcripts (XIST): long non-coding RNAs that coat X chr and initiates inactivation, induces methylation


Chromosomal aberrations detected by aCGH (microarray)

Copy number variations: deletions, duplications, insertional translocations, mosaicism (whole chr or segment), complex rearrangements.

Does not detect: balanced rearrangements, inversions, low level mosaicism


SNP arrays detect:

Uniparental disomy
Absence of heterozygosity
Loss of heterozygosity (cancer cells)
Identity by descent


Indications for SNP array

Suspected UPD/conditions associated w/imprinting.
Suspected AR condition due to common ancestry or consanguinity.
Determine parental origin of chr abnormality by trio analysis.

SNPs must exist/be known for gene of interest in order to be useful.


Indications for prenatal diagnosis (amnio/CVS)

1. AMA
2. Previous aneuploidy
3. Parental chr abnormality
4. Family history of diagnosable genetic disorder
5. Prior child or parent w/NTD
6. Abnormal screen
7. Abnormal U/S