Lecture 5 - Intro to Cytogenetics

Question 1

Role of cytogenetics

Answer 1

Identify chromosomal anomalies that may be associated with disease, contribute to diagnosis and treatment - “gold standard”

Question 2

Statistics of chromosomal abnormalities?

Answer 2

1/13 conceptions have one, only 6 in 1000 are born. 0.6% of newborns have chromosomal anomaly

Question 3

Do all chromosomal abnormalities appear early in life?

Answer 3

No, some may become obvious as the person ages

Question 4

What does one look for in chromosomal abnormalities?

Answer 4

Numerical (not 46 chromosomes) or structural - change in the size or shape of one of the chromosomes

Question 5

What specimens are needed to diagnose it?

Answer 5

Blood (DNA from leukocytes), amniotic fluid, chorionic villi, bone marrow (oncology), tissue

Question 6

Describe karyotype anaylsis

Answer 6

Compare chromosomes from metaphase in size, centromere position (metacentric, submetacentric, acrocentric), banding pattern

Question 7

Describe the parts of the chromosomes

Answer 7

P (short arm), Q (long arm), centromere connecting chromatids, terminated by telomeres.

Question 8

Describe an acrocentric chromosome

Answer 8

It has modified short arms with stalks containing only multiple copies of rRNA genes that are capped by a modified telomere called a “satellite”

Question 9

What is a banding pattern?

Answer 9

Chromosomes are stained after mild trypsinization and results in banding - each chromosome has a unique band pattern represented by an ideogram (pattern).

Question 10

Describe chromosome polymorphisms

Answer 10

the presence of two or more alternative structural forms for a chromosome within a population - inherited as Mendelian characters and can be traced. Not often associated with disease.

Question 11

Nomenclature for chromosomes

Answer 11

46,XX - normal female, 46,XY - normal male. 45,X/46,XX - mosaic

Question 12

Euploidy

Answer 12

exact multiples of the haploid set of chromosomes (3N and 4N not possible for life)

Question 13

Aneuploidy

Answer 13

gain or loss of chromosomes equaling less than one complete complement

Question 14

Trisomy

Answer 14

2N + 1 = 47 (Trisomy 13: 47,XX,+13) 47,XXY

Question 15

Monosomy

Answer 15

2N - 1 = 45 (Monosomy 8: 45,XY,-8) 45,X

Question 16

What are some ways aneuploidy may occur?

Answer 16

1. Nondisjunction in anaphase 1 of meiosis for 1 chromosome

2. Mitotic errors giving rise to some cells with 3 copies

Question 17

What is mosaicism?

Answer 17

The result of a mutation that leads to a unique finding in a second cell which establishes a second cell line. Usually the two cell lines differ by this single change. Mosaicism is ACQUIRED.

Question 18

What are some viable autosomal trisomies?

Answer 18

X, 13, 18, and 21

Question 19

Trisomy 21

Answer 19

1/700, short stature, low set ears, mental retardation, short hands, eye folds, protruding tongue. Multiple system defects (heart, lung, brain - huge range)

Question 20

Trisomy 13

Answer 20

Patau Syndrome - 1/4000-10000, failure to thrice, cleft lip/palette, rock bottom feet, polydactyly, heart defect

Question 21

Trisomy 18

Answer 21

Edwards Syndrome - 1/8000, low birth weight, small mouth jaw, hypoplasia of muscles, crossed fingers

Question 22

Sex chromosome aneuploidies

Answer 22

Klinefelter syndrome (47, XXY), XYY male, XXX female, Turner syndrome (45,X)

Question 23

Homogametic and hetergametic

Answer 23

Homogametic (females): have 2 copies of one type of chromosome (X chromosome)

Heterogametic (males): have 1 copy of 2 different types (X and Y)

Question 24

Describe X and Y chromosomes

Answer 24

Both have areas for recombination at tips, the “pseudoautosomal” region, under which is the TDF (testis determining factor) and SRY (sex determining region) which can occasionally be crossed over

Question 25

Describe the process of sex determination for a female

Answer 25

Female development is default - females lack the TDF/SRY, ovaries develop, proliferation of Mullerian ducts, regression of Wolffian ducts

Question 26

Sex determination for a male

Answer 26

TDF/SRY present, testes develop, inhibition of Mullerian ducts which ultimately degenerate. Testosterone produced >> Wolffian duct proliferation

Question 27

Describe the process of sex determination in general

Answer 27

Due to genes on the X, Y, and autosomes (TDF not the only factor). Occurs early in development, loss of sex chromosome later in life doesn't matter.

Question 28

Why are females not at a deficit with no Y?

Answer 28

Y chromosome involved mainly with male characteristics

Question 29

Why are males not at a deficit because of only 1 X?

Answer 29

X inactivation - Barr bodies in somatic cells of females shoes a condensed X chromosome. Happens 3-7 days after fertilization, needed for determination of normal female.

Question 30

Describe somatic mosaicism

Answer 30

If a female is heterozygous, then there will be subpopulations in her body. Some cells will express the traits on the maternal X and some will express traits on the paternal X. Ex - calico kitties!