Cytogenetics Flashcards
Aneuploidy
Monosomy: loss of a chromosome. Not compatible with life (except monosomy X/TURNER SYNDROME)
-kleinfelter syndrome (47, XXY)
Trisomy: presence of an additional chromosome.
- trisomy 21 (Down syndrome )
- trisomy 18 (Edward syndrome)
- trisomy 13 (Patau syndrome)
Euploidy (polyploidy) (number of chromosomes is in multiples of 23)
Triploidy: contain three copies of each chromosome (69). Not compatible with life
-observed in abortus (69, XXY)
Tetrapoidy: contain 4 copies of each chromosome (92). Lethal
-trisomy 21 (Down syndrome ), 47, XY, +21
Increase maternal age, increases risk of neurotic nondisjunction during oogenesis
-most common is meiosis 1 nondisjunction
trisomy 18 (Edward syndrome), 47, XY, +18
Nondisjunction during oogenesis.
Features:
- clenched fist, overlapping of fingers
- rocker bottom feet
- congenital heart defects
- low-set ears, micrognathia
- microcephaly
- Intellectual disability
Triscomy 13 (Patau syndrome)
Nondisjunction during oogenesis
Features:
- polydactyly
- cleft lip and palate
- microphthalamia
- microcephaly
- intellectual disability
- cardiac anomalies
Turner syndrome (45, X)
Nondisjunction during meiosis (x chromosome monosomy)
- short stature
- webbed neck, cystic hygroma at birth(neck swelling)
- Gonadal dysgenesis
- streak ovaries
- primary amenorrhea
Other cells are 46, XX and 47 XXX (indicate mitotic nondisjunction during embryogenesis)
Cells with 45 X; have no Barr body (inactivated X-chromosome)
Kleinefelter syndrome (47, XXY)
Nondisjunction during meiosis I or II in mom or nondisjunction in meiosis I in dad (XYY)
- testicular atrophy
- Gynecomastia
- female distribution of hair
- infertility 7
Tripoidy (3*23=69 chromosomes)
Observed in abortus
Tetraploidy
In cancer
5 Common Chromosomal Syndromes caused by nondisjunction
Trisomy 21 Trisomy 18 Trisomy 13 (Patau) Monosomy X 47, XXY
Structural chromosomal Abnormalities
- Balanced
- Unbalanced
- Balanced (No loss or gain of genetic material)
- Unbalanced (gain or loss of genetic material)
Translocation -Reciprocal -Robertsonian Deletions Inversions Ring chromosomes Isochromosome
Reciprocal Translocation
Exchange of genetic material between non-homologous chromosomes
-chromosome 2 and 8- balanced reciprocal translocation
In somatic cells:
- transformation to cancer occurs
- may have no effect ( silent)
In germline:
-may cause spontaneous abortion in carriers
Reciprocal Translocation in SOMATIC CELLS
- activation of an oncogene–>cancer
- Philadelphia chromosome t(9;22)–>activation of ABL protooncogene in hematopoietic cells–>results in chronic myelogenous leukemia
- t(8;14)–>Burkitt’s lymphoma
Robertsonian Translocation
Occurs between acrocentric chromosomes
-chromosome 13, 14, 15, 21, 22
Fusion of the long arms of the two chromosomes.
Effects during meiosis
Alternate segregation can result in
- Normal Gamete
- Gamete with derivative chromosome, that results in a Robertsonian translocation carrier on fertilization
Adjacent Segregation results in trisomy of the respective chromosome on fertilization.
- Trisomy 14 does not survive
- Accounts for 2-5% of children with Down syndrome mainly due to adjacent segregation
Segregation at meiosis
Alternate segregation
Adjacent I segregation
Adjacent II segregation
Microdeletion Syndrome
Large deletions >4Mb
- Wolf-Hirschhorn (4p-), Cri du Chat (5p-)-test with FISH
- may be detected by classical cytogenetic
Small Deletions (microdeletions) <4 Mb -FISH, Array CGH
Wolf-Hirschhorn Syndrome
- Deletion of chr 4p
- Facial anomalies widely spaced eyes, prominent nose, abnormal iris
- Cardiac anomalies
- Intellectual and developmental delay
Wilms’ tumor, Aniridia, genitourinary malformations, and retardation of growth and development (WAGR) Syndrome
Small-microdeletions
Deletions in Chromosome 15 (15q11)
Prader-Willi syndrome (Paternal deletion)
- hypotonia
- initial failure to thrive
- Distinctive facial features
- Developmental delay
- hypogonadism
- eating disorder
Angelman Syndrome (happy puppet)-maternal deletion -hypotonia' -seizures -lack of speech severe developmental delay -lack
Inversions
Pericentric: involves centromere
Paracentric: does not involve centromere
Usually balanced and no clinical problems in carriers
-result in a change in the banding pattern of the chromosome and can be identified by Karyotype analysis
Note: Chromosome with acentric (no centromere) and dicentric (2 centromere on one chromosome) are not viable.
Carriers maybe asymptomatic, but they have a high risk of spontaneous abortion.
Isochromosomes
- Loss of one arm of a chromosome, and duplication of the other arm.
- X isochromosome: long arms of the X chromsome join form an isochromosome
- Typically results in chromosomal and gene dosage imbalance
- Isochromosome is typically inactivated
e.g. some turner syndrome children
Ring Chromosomes
chromosome loses genetic material at the terminal portions and the ends fuse to form a ring like structure
