Cytogenetics Flashcards
diagnostic of CML and a subset of B-precursor ALL
t(9;22)(q34;q11.2)
AML-M2
t(8;21)(q22;q22)
acute promyelocytic leukemia (AML-M3)
t(15;17)(q22;q21)
B-precursor ALL
t(12;21)(p13;q22)
diagnostic of a subset of B-precursor ALL observed mostly in infants.
t(4;11)(q21;q23
Imprinting plays a major role in the phenotype of
Angelman syndrome, Prader-Willi syndrome, Beckwith-Wiedmann syndrome, Russell-Silver syndrome, ovarian teratoma, and triploidy.
The probability that a trisomy 21 conception will result in live birth
approximately 20%.
Allelic heterogeneity
the situation when different alleles of a single gene produce different phenotypes
Incomplete penetrance
the situation when an individual has a genotype known to cause a disease but does not display a phenotype.
Locus heterogeneity
he production of identical phenotypes by mutations at two or more different loci
Pleiotropy
a single gene or gene pair causes multiple phenotypes, especially when the effects are not obviously related
Expressivity
the extent to which a genetic defect is expressed, from mild to severe.
Detection of confined placenta mosaisism
CVS samples chorionic villi from the placenta and can detect the mosaicism. The other tissues sampled do not include placental cells and will not allow for detection of mosaicism confined to the placenta.
Potocki-Lupski
the only syndrome listed that is mediated by NAHR
1p36 deletion syndrome
not NAHR
Cri du Chat syndrome
not NAHR
Miller-Dieker syndrome
not NAHR
Wolf-Hirschhorn syndrome
not NAHR
Order of cytogenetics treatments
-lymphocytes are stimulated to a blast phase with the red kidney bean extract phytohemagglutinin (PHA). After 48-72 hours, a mitotic poison such as Colcemid or colchicine is used to block spindle formation and attachment to “arrest” cells in mitosis, a hypotonic treatment is used to swell the cells, they are fixed in 3:1 methanol:acetic acid, put onto slides, and then most often treated with trypsin prior to Giemsa staining to produce G-banding patterns.
Balanced chromosomal rearrangement
A balanced parental insertion can result is an offspring with either a balanced karyotype (normal karyotype and balanced insertion) or an unbalanced karyotype (interstitial deletion or duplication)
Balanced paracentric inversion
The recombinant chromosome products are either acentric or dicentric and are usually nonviable
Balanced pericentric inversion
recombinant chromosome with a terminal duplication involving one chromosome arm and a terminal deletion involving the other arm
Robertsonian translocation
An acrocentric chromosome trisomy
Female carriers of the 14;21 Robertsonian translocation
The risk of having a trisomy 21 offspring in female carriers of the 14;21 Robertsonian translocation is ~10-15%, whereas the risk in male carriers is ~0-2%
Larger pericentric inversions vs. small for risk of unbalanced offspring
Carriers of large pericentric inversions have higher risk than small pericentric inversions.
Risk of unbalanced offspring for balanced autosomal translocation
Carriers of balanced autosomal translocations have a 10-15% risk of having unbalanced offspring
Risk of trisomy 21
Carriers of the 21;21 Robertsonian translocation have a 100% risk of having trisomy 21 offspring.
the most common recurrent microdeletion syndrome?
22q11 deletion syndrome–including DiGeorge syndrome and VCF (velocardiofacial syndrome) is the most common deletion syndrome in humans, occurring in ~1/4000 births. This is a common, recurrent microdeletion mediated by NAHR of flanking low-copy repeats (LCRs). Other LCR genomic disorders (PWS, AS, Williams, Smith-Magenis, Sotos) occur at ~1/10,000-1/20,000. Random deletion syndromes such as cri du chat, Wolf-Hirschhorn, Miller-Dieker syndrome, retinoblastoma, aniridia-Wilms tumor are less common (1/50,000-1/100,000 or less).
Diandric triploidy
the most common type of triploidy. It presents with a large cystic placenta with molar changes (partial hydatidiform mole). The fetus is usually proportionate or has a slightly small head size. Other features include syndactyly of 3rd and 4th fingers, incomplete ossification of the skull, and many other congenital anomalies
Recurrence of triploiod pregnancy
A triploid pregnancy does not have an increased recurrence risk in future pregnancies
Digynic triploidy
less common and usually results in early spontaneous abortion with very small and fibrotic placenta. If a fetus is present, it usually has macrocephaly. Other features also include syndactyly of 3rd and 4th fingers, incomplete ossification of the skull, and many other congenital anomalies
Triploid pregnancies
Polyploid pregnancies collectively constitute approximately 20% of chromosomally abnormal first trimester spontaneous abortions
Adjacent segregation 1
- Adjacent segregation-1 is when homologous centromeres segregate
- adjacent-2 where the homologous centromeres go to the same cell. Adjacent-2 is rare compared to adjacent-1.
Parental cause of Trisomy 16
Trisomy 16 is a prenatal lethal aneuploidy due to a maternal meiosis I nondisjunction in 100% of cases
Parental origin of Turner syndrome
Turner syndrome (45,X) is 70% paternal and 30% maternal in origin
Only one where paternal origin is more likely to cause
Parental origin of Trisomy 21
92% maternal and 8% paternal in origin
47,XXX parental origin
47,XXX is 90% maternal and 10% paternal in origin
Parental origin of Klinefelter syndrome (47,XXY)
54% maternal and 46% paternal in origin.
A 10 year old male presents with mild glove and stocking sensory loss, depressed reflexes, and pes cavus
17p12 duplication that encompasses the PMP22 gene.
The phenotype of the patient and the 17p12 duplication is consistent with the clinical diagnosis of Charcot-Marie-Tooth syndrome type 1A (CMT1A)
Staining types
R-bands are the reverse of G-bands, so there are the same number of each. G-positive bands are AT-rich and relatively later replicating.
A 2-year-old boy presents with a history of retinoblastoma, dysmorphic features and developmental delay. Which of the following molecular abnormalities is the most likely cause of his clinical findings?
Contiguous gene deletion of 13q14
Microarray analysis could help to
identify the origin of a marker chromosome (A) or additional material on a chromosome (D), look for an imbalance at the breakpoint of an apparently balanced de novo translocation (C), or define the size and gene content of an unbalanced translocation (E).
Not examine 47,XX,+21
WAGR syndrome
11p- deletion is associated
Wolf-Hirschorn syndrome
4p- syndrome
Historical Cytogenetics timeline
- The discovery of the Y Chromosome and the XX/XY mechanism of sex determination in humans was by T. S. Painter in 1923,
- hypotonic treatment of cells by T. C. Hsu in 1953,
- the correct chromosome number by Tjio and Levan in 1956,
- chromosome banding techniques in 1969/70,
- and fragile sites and fragile X in the late 70s.
patients with trisomy 13
the clinical picture that includes IUGR and FTT, microcephaly, microphthalmia, iris coloboma, cleft lip/palate, holoprosencephaly, scalp defect, postaxial polydactly, renal and GI anomalies, omphalocele, and congenital heart defects
colomboma
Hole in the iris associated with gene PAX2
- CHARGE syndrome
- Cat eye syndrome
- Patau syndrome
- Teacher Collins syndrome
- Tilted Disc Syndrome
