Lecture 5 - Intro to Cytogenetics Flashcards
Role of cytogenetics
Identify chromosomal anomalies that may be associated with disease, contribute to diagnosis and treatment - “gold standard”
Statistics of chromosomal abnormalities?
1/13 conceptions have one, only 6 in 1000 are born. 0.6% of newborns have chromosomal anomaly
Do all chromosomal abnormalities appear early in life?
No, some may become obvious as the person ages
What does one look for in chromosomal abnormalities?
Numerical (not 46 chromosomes) or structural - change in the size or shape of one of the chromosomes
What specimens are needed to diagnose it?
Blood (DNA from leukocytes), amniotic fluid, chorionic villi, bone marrow (oncology), tissue
Describe karyotype anaylsis
Compare chromosomes from metaphase in size, centromere position (metacentric, submetacentric, acrocentric), banding pattern
Describe the parts of the chromosomes
P (short arm), Q (long arm), centromere connecting chromatids, terminated by telomeres.
Describe an acrocentric chromosome
It has modified short arms with stalks containing only multiple copies of rRNA genes that are capped by a modified telomere called a “satellite”
What is a banding pattern?
Chromosomes are stained after mild trypsinization and results in banding - each chromosome has a unique band pattern represented by an ideogram (pattern).
Describe chromosome polymorphisms
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.
Nomenclature for chromosomes
46,XX - normal female, 46,XY - normal male. 45,X/46,XX - mosaic
Euploidy
exact multiples of the haploid set of chromosomes (3N and 4N not possible for life)
Aneuploidy
gain or loss of chromosomes equaling less than one complete complement
Trisomy
2N + 1 = 47 (Trisomy 13: 47,XX,+13) 47,XXY
Monosomy
2N - 1 = 45 (Monosomy 8: 45,XY,-8) 45,X
What are some ways aneuploidy may occur?
- Nondisjunction in anaphase 1 of meiosis for 1 chromosome
2. Mitotic errors giving rise to some cells with 3 copies
What is mosaicism?
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.
What are some viable autosomal trisomies?
X, 13, 18, and 21
Trisomy 21
1/700, short stature, low set ears, mental retardation, short hands, eye folds, protruding tongue. Multiple system defects (heart, lung, brain - huge range)
Trisomy 13
Patau Syndrome - 1/4000-10000, failure to thrice, cleft lip/palette, rock bottom feet, polydactyly, heart defect
Trisomy 18
Edwards Syndrome - 1/8000, low birth weight, small mouth jaw, hypoplasia of muscles, crossed fingers
Sex chromosome aneuploidies
Klinefelter syndrome (47, XXY), XYY male, XXX female, Turner syndrome (45,X)
Homogametic and hetergametic
Homogametic (females): have 2 copies of one type of chromosome (X chromosome)
Heterogametic (males): have 1 copy of 2 different types (X and Y)
Describe X and Y chromosomes
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
Describe the process of sex determination for a female
Female development is default - females lack the TDF/SRY, ovaries develop, proliferation of Mullerian ducts, regression of Wolffian ducts
Sex determination for a male
TDF/SRY present, testes develop, inhibition of Mullerian ducts which ultimately degenerate. Testosterone produced»_space; Wolffian duct proliferation
Describe the process of sex determination in general
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.
Why are females not at a deficit with no Y?
Y chromosome involved mainly with male characteristics
Why are males not at a deficit because of only 1 X?
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.
Describe somatic mosaicism
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!
