Variations In Chromosone Number Flashcards
How are chromosomes treated with chemicals to view patterns
First the fixed chromosomes on a slide are treated with trypsin so that the DNA loosens up bit
-trypsin is a protease which, when used for a short time will partially digest proteins associated with the chromosome
- Next, the fixed chromosomes are stained with a purple dye called Geimsa
- some regions of the chromosomes pick up more dye resulting in a banding pattern
-The pattern of staining is viewed under the microscope and photographed
What can cause variations in two haploid sets?
- Change in total number of chromosomes
- Deletion or duplication of genes/segments of chromosome
- Rearrangements of genetic material within or among chromosomes
What is aneuploidy?
- Variations in chromosome number
- Organism gains or loses one or more chromosomes(not entire set)
What are the types of aneuploidy?
Monosomy
Trisomy
Polyploidy
Euploidy
Triploid
What is Monosomy?
Loss of single chromosome in diploid genome
What is trisomy?
Gain of single chromosome
What is euploidy?
Complete haploid sets of chromosomes are present
What is polyploidy?
More than two sets of chromosomes are present
What is triploid?
Three sets of chromosomes
How can triploidy(3n) happen?
- Most common cause is dispermy (one egg and two spermatozoa)
- Could be fertillization of a primary oocyte
- Could be a failure to separate homologous chromosomes in Meiosis 1
- Could be a failure to separate homologous chromosomes in Meiosis II
- Could be retention of a polar body
How often does triploidy (3n) occur?
Occurs in 2-3% of conceptuses and ~ 20% of chromosomal abnormal first-trimester miscarriages
How can tetraploidy(4n) happen?
- Rare occurrence, may be chromosome separation failed during meiosis 1 or II in the egg cell and then dispermy
- Failed sister chromatid separation in an early embryo
What is nondisjunction ?
Failure to separate
- Gives rise to chromosomal variation
- Paired homologs fail to disjoin during segregation
- Nondisjunction during meiosis 1 or II
What can result from Monosomy?
- Loss of one chromosome
- Produces 2n-1 complement
- Haploinsufficiency: when one copy is not sufficient for organism to survive
Loss of sex chromosomes is compatible with life
46, XX loss of X= 45,X. 47,XY loss of Y= 45, X
Turner Syndrome
Contrast the effect of a loss of sex chromosome and loss of autosomes
- Loss of any one of the autosomes is not compatible with life
- loss of a sex chromosome IS compatible with life
What are the effects of trisomy of autosomes?
2n+1 chromosomes
Most trisomy involving the autosomal chromosomes are lethal
Three exceptions which result in live-born children
- trisomy 21(Down syndrome)
- trisomy 18(Edward syndrome)
- trisomy 13 (Patau Syndrome)
What disease results from trisomy 21?
Down syndrome
What disease results from trisomy 18?
Edward syndrome
What disease results from trisomy 13?
Patau syndrome
Differentiate trisomy and triploidy
Triploidy-extra chromosome added to each pair resulting in 69, XXX or 69, XXY or 69, XYY
Trisomy adds an extra chromosome to a single pair (e.g. chromosome 21 pair gets gets another to cause Down syndrome) 47, XX or 47, XY
What is the frequency of Down syndrome?
1: 800 live births
What is the life expectancy of a person with Down syndrome?
Live expectancy on average is about 60 years
What are the phenotypic characteristics of Down syndrome?
- short stature
- depressed nasal bridge
- upslating palpebral fissures
- Brushfield spots on iris of the eye
- Epicanthal folds (skin fold from the nose to upper eyelid)
- short neck
- low-set small, folded ears
Aside from phenotypic characteristics, how may down syndrome affect an individual?
- Intellectual disability and heart malformations
- affected individuals bear a striking resemblance to one another
Where is the down syndrome critical region?
- critical region of chromosome 21
- Cytogenic location 21q22
- 1.6 Mb region
- thought to be responsible for some of the combebsck
Aside from cytogenic location 21q22, what other genes are responsible for Down syndrome?
Other genes in chromosome 21 thought to be responsible for features of Down Syndrome
- APP(amyloid precursor protein) -Alzheimer’s disease
- AML1 (acute myeloid leukemia 1) -Leukemia
What is the most common occurrence of nondisjunction?
Most common origin is nondisjunction of chromosome 21 during oogenesis at meiosis I
-estimated to account for 75% of cases
What is the second most common origin of nondisjunction?
Second most common origin of nondisjunction during oogenesis at meiosis II
- about 20% of cases
Why is there increased risk of extra 21st chromosome with maternal age?
- Meiosis 1 is initiated in all the eggs of a female while she is a fetus
- Oocyte development is arrested in meiosis 1 where synapses are formed and recombination has begun
- At ovulation, beginning at female puberty, meiosis is reinitiated in one egg and continues to meiosis 2
- the process is again arrested after ovulation and is not complete till fertillization.
THE OLDER THE FEMALE, THE LONGER THE OVA HAVE BEEN ARRESTED IN METAPHASE 1
How does maternal age correlate to extra 21st chromosome?
Increased risk with increased maternal age
Is Down syndrome inherited?
Familial Down syndrome is inherited and runs in families
Involves a process called translocation
1-5% of Down syndrome is inherited
What are the features of Trisomy 18 (Edward syndrome)
- Clenched fist, overlapping of fingers
- Rocker bottom feet
- Congenital heart defects
- Low-set ears, small lower jaw (micrognathia)
- Microcephaly (small head)
- Intellectual disability
What is the genetic mechanism of trisomy 18?
Genetic mechanism is nondisjunction during oogenesis
What are the features of trisomy 13?
Features:
- Polydactyl (extra fingers and toes)
- Cleft lip and palate
- Microphthalmia(small eyes)
- Microcephaly (small head)
- Intellectual disability
- Cardiac anomalies
What is the most common mechanism of trisomy 13?
Most common genetic mechanism is nondisjunction during oogenesis
What is the karyotype of trisomy 13?
47, XX, +13
What is Mosaicism ?
Less severe presentations of trisomies a than other presentations, such as some babies having 15/ 20 cells have trisomy (75% mosiacism)
Explain the first theory of Mosaicism?(miotic nondisjunction)
Non-disjunction May occur as a post-zygotic event during embryonic development; that is mitotically (after fertillization of a normal ovum and normal sperm)
This will lead to 2 cell types:
- One continues as normal karyotype
- the other with trisomy 21
Explain the second theory of Mosaicism? (Trisomy rescue)
- Non-disjunction May occur in the ovum during oogenesis, and fertilization a normal sperm leads to trisomy 21 in the conception
- During a post-fertilization mitosis, one of the extra chromosome 21 is evicted during cell division
- Now the fetus has 2 cell types, one with normal karyotype, and one that is trisomy 21
How can trisomy rescue lead to uniparental disomy ?
-trisomy of autosomal chromosomes (except 13, 18 and 21) are not compatible with life
- theory that fertilizedess will survive to develop an embryo if one of the extra chromosomes is removed
- 30% chance of giving rise to uniparental disomy
