MCP 2 Flashcards
1. discuss the principle of mitosis, meiosis and gametogenesis 2. describe the chromosomal basis of inheritance and the basic structure of chromosomes 3. explain sex determination and to have a working knowledge of X inactivation and reactivation
Cytogenetics
the science that combines the methods and findings of cytology and genetics
-the study of heredity at the cellular level
Cell cycle
somatic division = mitosis (2N)
germ division = meiosis (N)
Mitosis
phases: interphase, prophase, metaphase, anaphase and telophase -> followed by cytokinesis and separation of the materials into two new daughter cells (genetically identical to the parent cell)
What is the most important mitotic phase for cytogenetics?
metaphase
Meiosis
-occurs in the gonads
Meiosis I -> prophase I (recombination) -> metaphase I -> anaphase I (reduction division) -> telophase I –>Meiosis II-> metaphase II -> anaphase II -> telophase II
Recombination
-results when two homologs break and exchange places (crossing over) ->an exchange between homologous chromosomes resulting in re assortment of the genes/alleles present on each chromosome
nondisjunction
failure of the chromosomes or chromatids to disjoin properly - meiosis nondisjunction can occur at either the first or second division and net result is different
Disomy
the presence of 2 chromosomes
Isodisomy
2 chromosomes from the same source ==> duplication of 1 chromosome
Heterodisomy
2 different chromosomes
Result of meiotic nondisjunction I
- two disomic (heterodisomic)
- two nullsomic
Result of meiotic nondisjunction II
- one disomic (isodisomy)
- one nullsomic
Oogenesis
- oogenesis begins in the developing fetus
- by the third month of gestation all of the primary oocytes are present
- these cells reach dictyotene (prophase I) by birth and remain there until ovulation
- at ovulation the oocyte completes meiosis I and becomes a secondary oocyte
- meiosis is only completed if fertilization occurs
Sex chromosomes
- the X and Y chromosomes
- of 46 chromosomes (23 pairs) -> 22 autosomal pairs and 1 pair of sex chromosomes
What is the default gender development pattern in humans?
Female
Once the sex of an individual has been determined, loss or gain of key genes or sex chromosomes
is clinically irrelevant
Sex determinations
is due to genes on the X, Y and autosomes
occurs very early in development
Lyon Hypothesis
- one X is inactivated in somatic cells of females -> called bar bodies appear as dark stain dot
- total number of bar bodies = total number of chromosomes - 1
- for normal female there must be two active X chromosomes
- inactivation occurs early in development, 3-7 days after fertilization
- inactivation is random, but once established is not reversible in SOMATIC tissues
- X inactivation results in dosage compensation - so that boys can only have one and are the same as girls
Dosage compensation
equalization of the amount of active genetic material
If a female is a heterozygote
she will be a mosaic -> somatic mosaicism -> some cells in her body will express the maternal X and some will express the paternal X
Non-random X inactivation
results when there is an abnormal X chromosome present that is preferentially inactivated -> skewing the distribution such that the alleles on the other X are always expressed
Mechanisms of X inactivation
- epigentic
- methylation -XIST (x inactivation center)
- several sites appear to escape inactivation- including the pseudoautosomal region
- inactive X must be reactivated at meiosis so that active Xs are transmitted to offspring
Clinical role of cytogenetics
- identify chromosomal anomalies that may be associated with disease
- contribute to the diagnosis and treatment of patients
- individuals of all age groups
- many different diseases
- effect of chromosomal abnormalities: change in phenotype, fetal loss, genetic disease, malignancy
Fetal Loss
- 1/13 conceptuses with chromosomal abnormality -> 6/10,000 born live
- 15% of recognized pregnancies end in spontaneous abortion-> 80% first trimester
- of spontaneous loss -> 60% chromosomal
- of chromosomal losses 52% are autosomal trisomies
Post-natal role of cytogenetics
- about 0.6% of newborns have a chromosome anomaly
- ambiguous genitalia
- multiple congenital anomalies
- features of chromosomal disorder
What two categories do most cytogenetically detectable abnormalities fall into?
-structural
-numerical
then its important to figure out precisely which gene
Potential specimens for cytogenetics
- blood (easiest)
- amniotic fluid (prenatal)
- chorionic villi (prenatal)
- bone marrow (oncology)
- tissue (skin- when deceased)
How do we identify chromosomal abnormalities?
karyotype analysis - chromosomes arrested at metaphase (hence why its the most important)
- size
- centromere position
- banding pattern
Metacentric
when the centromere is located approximately equidistant from each half of the chromosomes
Submetacentric
when centromere is closer to one end than the other
Acrocentric
chromosome has modified short arms with stalks containing only multiples copies of rRNA genes that are capped by a modified telomere called a satellite
what is the total number of chromosomes defined by?
The number of centromeres
telomere
end of the chromosome- regions are known to be composed of tandem repeated DNA with the sequence (TTAGGG)n -shorten with each replication, have been thought to be implicated in aging process
Banding pattern
each pair of chromosomes has a unique banding pattern that can be used to identify -> comes from DNA trypsinization weakens prior to staining then stained with either Giemsa or Wrights stains which are positive to attract to negatively charged DNA
Chromosomal polymorphism
the presence of two or more alternative structural forms for a chromosome within a population
- inherited as Mendilian traits and can be traced through pedigrees
- are usually not associated with clinical anomalies or particular diseases
