Genetics1.numerical Chromosome Abnormalities.mcv/vcu

Front 1

Define the terms:
a. Euploid
b. Nondisjuction
c. Aneuploid

Back 1

A. Euploid - an exact multiple of the number of chromosomes in a normal haploid gamete (n). Most somatic cells are diploid (2N).

B. Nondisjunction - failure of a chromosome pair to disjoin during MI (meiosis 1) or 2 chromatids to separate in MII (meiosis 2) or mitosis

C. Aneuploid - any chromosome number that is not an exact multiple of the haploid number (example: trisomy or monosomy).

Front 2

Define the terms:
d. Trisomy
e. Monosomy
f. Mosaicism

Back 2

D. Trisomy - the state of having an additional copy of a chromosome (3 copies rather than 2) (e.g. Trisomy 21).

E. Monosomy - a chromosome constitution in which one member of a chromosome of a pair is missing (e.g. 45,X).

F. Mosaicism - a condition in which an individual has 2 or more genetically distinct cell lines derived from a single zygote

Front 3

Frequency of Chromosome Aberrations in Newborn Survey

Back 3

Ranking of chromosome aneuploidy

trisomy 21> balanced structural rearrangements > sex chromosome aneuploidies including 47,XXX; 47,XXY, and 47,XYY.

Front 4

Trisomy 21 (Down Syndrome)
Male:Female Ratio 3:2

What are the clinical findings?

Back 4

· Mental retardation (IQ 25-50)
· *Low nasal bridge (90%)
· *Hypotonia (80%)
· *Upslanting palpebral fissures (80%)
· Small, low set ears (60%)
· *Congenital heart disease (30%50%)**
· *Simian line (transverse crease) (45%)
· *Epicanthic folds (epicanthus is a skin fold of the upper eyelid)
· Protruding tongue
· Intestinal problems
· Gap between first and second toes
· 15 fold increase in risk for leukemia

Front 5

Trisomy 18 (Edward's Syndrome)
Male:Female Ratio 1:4
10% of affected individuals surviving beyond the first year

What are the clinical findings?

Back 5

· Congenital heart disease in 95%
· Failure to thrive
· Mental retardation (More severe than Down Syndrome)
· *Growth retardation
· *Hypertonia
· *Prominent occiput
· *Microretrognathia (recession of jaws [mandible])
· *Low set malformed ears
· Short sternum
· Intestinal abnormalities
· *Unusual hand position
· *Rocker bottom feet

Front 6

Trisomy 13. (Patau syndrome)
Lethal in nearly all cases by the age of six months.

What are the clinical findings?

Back 6

· *Congenital heart disease in 85%
· Mental retardation
· Hyper- or hypotonia
· *Scalp defects
· *Microcephaly
· Small eyes
· *Low set malformed ears
· *Cleft lip/palate
· *Polydactyly and syndactyly
· Polycystic kidneys
· Rockerbottom feet

Front 7

Explain Numeric Abnormalities Among Spontaneous Abortuses/Gametes, and which is the most common?

Back 7

Unbalanced chromosome abnormalities are more frequent in spontaneous abortuses (~30%50% of abortuses or 10% of first trimester embryos) than newborns (~ 0.6%).

Trisomy 16 is the most common trisomic abnormality

Monosomy X is also frequently seen

Front 8

How does Triploidy 69 chromosomes occur?

Back 8

Occurs from two sperm fertilizing a single egg (dispermy), or failure of meiotic divisions in the egg or sperm. Fetus phenotype influenced by parental source of extra chromosome set.

Paternal complements associated with proliferation of the placenta and a wellgrown fetus w/wo microcephaly.

Maternal do not demonstrate the same placental proliferation. Severe intrauterine growth retardation with relative macrocephaly.

Front 9

What are the clinical findings of Triploidy 69?

(Of triploid fetuses born alive, all are characterized by gross and multiple malformations. They live for only a few hours.)

Back 9

· Enlarged placenta (diandric)
· Hydatidiform placenta cystlike (diandric)
· Heart Abnormalities
· Kidney anomalies
· Low set malformed ears
· Hypertelorism
· Macroglossia (enlargement of tongue)
· Foot Deformities
· Abdominal wall defects
· Macrocephaly (Digynic)
· Severe intrauterine growth retardation (Digynic)

Front 10

What are the nondisjuction errors in Meiosis?

Back 10

A. Meiosis I: failure of reduction division such that the homologous chromosomes segregate together.

B. Meiosis II: failure of chromatids to separate

Front 11

Causal Factors in Nondisjunction

Back 11

1. Parental origin of the extra chromosome in trisomy 21.
-maternal errors account for 94% of cases
-Determined through structural staining characteristics (variants or heteromorphisms) or molecular markers

2. Advanced maternal age

3. recombination abnormalities

4. Interchromosomal interactions

Front 12

Recombination abnormalities

Back 12

Disturbances in the rate of recombination (either too little or too much) may lead to erroneous segregation.

Front 13

Interchromosomal interactions

Back 13

Interactions (or possibly pairing) between similar genetic sequences on different (nonhomologous) chromosomes may contribute to the improper segregation of homologous chromosome.