W2LECT - CYTOGENETICS Flashcards
What is CYTOGENETICS?
Study of chromosomes
Clinical indications for chromosome analysis
1. What are the 5 clinical indications for chromosome analysis?
- Problems of early growth and development
- Stillbirth and neonatal death
- Infertility
- Pregnancy in a woman of advanced age
- Family history
- Cancer
Clinical indications for chromosome analysis
2. What are the Problems of early growth and development that need to be seen in chromosome analysis?
eg. developmental delay, dismorphic face, multiple malformations, mental retardation are frequent findings in children with chrom. abnormalities.
Clinical indications for chromosome analysis
3. Why is Infertility a clinical indications for chromosome analysis?
Women with amenorrhea, couples with a history of infertility or habitual abortion.
Clinical indications for chromosome analysis
4. Why is Pregnancy in a woman of advanced age a clinical indications for chromosome analysis?
there is an increased risk of chromosome abnormality in fetuses of mothers older than the age of 35 years – prenatal diagnosis
Clinical indications for chromosome analysis
5. Why is Family history a clinical indications for chromosome analysis?
known or suspected chrom. abnormality in a first degree relative
Clinical indications for chromosome analysis
6. Why is Cancer a clinical indications for chromosome analysis?
virtually all cancers are associated with one or more chrom. abnormalities.
What are the 2 main types of CHROMOSOME ABERRATIONS?
- Numerical disorders - genome mutation
- Structural disorders
CHANGES IN CHROMOSOME NUMBER
1. What are the 4 consequences of changes in chromosome number?
- Euploidy
- Polyploidy
- Aneuploidy
- Mixoploidy
CHANGES IN CHROMOSOME NUMBER
2. What is Euploidy?
Each chromosomes are in the same copy in the cell
CHANGES IN CHROMOSOME NUMBER
3. What is Polyploidy?
Changes in whole chromosome sets: multiplication
(ABNORMAL in human = there are more than two chromosome sets)
CHANGES IN CHROMOSOME NUMBER
4. What is Aneuploidy?
Changes in parts of chromosome sets (2n-1=monosomy; 2n+1=trisomy)
CHANGES IN CHROMOSOME NUMBER
5. What is Mixoploidy?
If only some of the body’s cells carry the extra set of chromosomes
Non-disjunction during meiosis
-> What is happening here?
What is the Consequence of meiotic non-disjunction?
Describe the differences in gametogenesis between male and female?
What are the dental aspects of Down syndrome?
- underdevelopment or hypoplasia of the midfacial region
- delayed emergence of the permanent teeth
- Severe crowding
- Hypodontia: high rate of missing teeth
- Microdontia
How does Down syndrome affect dental aspect in childhood?
In childhood incidence of caries is low
- increased spacing between teeth
- Alkaline saliva
How does Down syndrome affect dental aspect in adulthood?
high rate of periodontal disease: bw 90 and 96% in adults
- Immunodeficiency
What does trisomy 21, trisomy 18, trisomy 13 mean?
- Trisomy 21 - Down synsdrome
- Trisomy 18 - Edwards syndrome> In general perinatally lethal
- Trisomy - Patau syndrome (13/236) syndrome (17/145) -> In general perinatally lethal
Autosomal monosomy is lethal in __
utero
Why does the excess of chromosomes induce severe symptoms?
- Normal development and function depend on interactions between gene products, including many that are encoded on different chromosomes.
- Altering the relative numbers of chromosomes will affect these interactions, and cause imbalance.
What are numerical aberrations of sex chromosomes?
- Abnormalities are more tolerated
- If have extra Y: few genes mainly for sex determination
- If have extra X: excess X is inactivated
What does this picture show? Explain
47 XXY - Klinefelter syndrome
1. Feminine physical features
2. Hypogonadism, microorchidism – lack of secondary sexual characteristics
3. Gynecomastia
What are Periodontal symptoms of Klinefelter syndrome?
- Tooth size and enamel thickness is directly related to the number of extra X chromosomes:
- Maxillar and mandibular prognathism, Macrodontia,
taurodontism
What are the symptoms of 47 XYY - “superman”?
- No physical malformation: Very tall and thin
- Normal male gonads and sexual development
- Learning and behavioral difficulties
- Normal IQ
What are the symptoms of 47 XXX - “superwoman”?
- No physical malformation: Less feminine features, tall and thin
- Learning and behavioral difficulties
- Normal IQ
Describe Turner syndrome
a. X0 - Turner syndrome – onliest monosomy in newborns
b. Symptoms
- Short body height - hypothyroidism
- low hairline – neck webbing
- gonadal dysfunction –amenorrhea- sterility
- Congenital heart disease
- Normal IQ
What are Periodontal manifestations in Turner syndrome?
- high-arched palate
- Reduced tooth size
- Thinner enamel
- Tooth mobility
POLYPLOIDY
1. What is happening here?
- Triploidy 3n
- Tetraploidy 4n
What is happening here?
DNA duplication but no cell division
= ENDOMITOSIS
What is Diploid-triploid mosaic?
46, XY/69, XXY
What is happening here?
MIXOPLOIDY
What are the 2 consequences of mixoploidy?
- Abnormal mitosis => MOISAIC
- Two or more cell lines with different origin within one organism => CHIMERA
Describe chimerism?
eg. true hermaphroditism: 46XX/46XY 200 human cases
the presence of two genetically distinct cell lines in one organism
Skin is covered in stripes known as Blaschko’s lines are invisible and can often seen in UV light
Why is pregnancy a natural microchimerism?
Fetal microchimerism in the mother
Maternal microchimerism in the fetus
What is MOZAICISM?
One individual from a single zygote cells with different karyotype
What is the percentage of Chrom 21 Mosaictrisomy?
~ 2%
What are the 2 types of structural chromosomal abberations (1 - 3 breaks)? Describe them
- Lost
- Severe symptoms
- Usually lethal
- Unbalanced karyotype - Rearrangement
- Amount of genetic content doesn’t change
- Milder symptoms:
Affected individual is viable and usually has normal phenotype
- Balanced carrier
What are the 2 types of structural chromosomal abberations (1 - 3 breaks)? Describe them
- Lost
- Severe symptoms
- Usually lethal
- Unbalanced karyotype - Rearrangement
- Amount of genetic content doesn’t change
- Milder symptoms:
Affected individual is viable and usually has normal phenotype
- Balanced carrier
What are the 6 types of structural chromosomal abberations?
- Deletion
- Duplication
- Translocation
- Inversion
- Ringchromosome
- Isochromosome
What is the source of structural chromosome-aberrations?
Homologous recombination of repetitive sequences
What are the consequences of terminal deletion?
clinical features : cat-like cry,
mental retardation, microcephaly, hypertelorism and epicanthic folds
What is the cause of cri du chat syndrome?
- chromosome short arm
What is the consequence of partial deletions on the short arm of chromosome 5?
The cat-like cry is the most prominent clinical characteristic in newborn children and is usually considered as diagnostic for the CDC syndrome
What is Oral manifestation of Cri-du-chat syndrome?
- Significant oral anomalies: mandibular retrognathia
- retardation of tooth eruption
- enamel hypoplasia
- abundant plaque and gingivitis
- Periodontitis
What are the consequences of unequal crossing over?
- Deletion
- Duplication
What is muscular atrophy?
Inherited peripheral neuropathy– different dose of peripheral myelin protein (PMP22)
What are the characteristics of RINGCHROMOSOME?
- Following deletion of telomeres
- Severe consequencies :
DNA replication is abnormal
What are the characteristics of ISOCHROMOSOME?
- Sister chromatids abnormally segregate (perpendicular to the length)
- The loss of the complete arm
- Often lethal due to the loss of many genes
- Exception: Inactivated X chromosome, Gene poor Y chromosome
What are the characteristics of Translocation/ Inversion?
- Breakpoints are usually located at NON-CODING areas (coding regions ~2%)
- No chromosomal material has been lost or gained
- carriers of a balanced reciprocal translocation/inversion do not have any symptoms
What is the exception of Translocation/ Inversion?
Reciprocal translocations with breakpoints within genes
-> abnormal gene- product – often tumor formation even in balanced carriers
TRANSLOCATION
1. What are the 3 types of translocation?
A. Insertion
B. Reciprocal translocation
C. Robertsonian translocation (centric fusion)
TRANSLOCATION
2. What’s the Possible consequence of translocation?
oncogenic fusion protein (examples)
What is CHROMOSOMAL REARRANGEMENT?
Carriers with balanced translocation/inversion are at risk of producing offspring with part of one chromosome missing and part of another extra.
If there is CHROMOSOMAL REARRANGEMENT
=> What happens in meiosis? What kinds of gametes are formed?
Gametes are : normal, Balanced, abnormal
How does Meiotic segregation of reciprocal translocation?
Instead of 2 chromosomes (1 pair)
=> 4 chromosomes are joining
What happen to Offsprings of parents with balanced Robertsonian translocation?
INVERSION
1. What are the 2 types of inversion?
- Pericentric inversion
- Paracentric inversion
INVERSION
2. What is Pericentric inversion?
Inversion involves centromere
INVERSION
3. What is paracentric inversion?
Inversion restricted to chromosome arm
INVERSION - Meiotic segregation of inversion
4. What are the characteristics of paracentric and peri centric inversion loops?
Paracentric: inversed segment that does not include the centromere
Pericentric: inversed segment that includes the centromere
STRUCTURAL ABERRATION OF SEX CHROMOSOMES
1. What do Regions close to telomeres in Y and X chromosomes consist?
pseudoautosomal regions PAR1 and PAR2: genes match to each other
STRUCTURAL ABERRATION OF SEX CHROMOSOMES
2. Describe sex reversal in man?
a. 46 XX man
b. SRY bearing X
c. SRY translocation to X
d. The gonadal sex : male, testes
e. can not make viable sperm
STRUCTURAL ABERRATION OF SEX CHROMOSOMES
3. Describe sex reversal in woman?
- 46 XY woman
- SRY is lost
SRY deletion - The gonadal sex: female, reduced ovaries
- can not make viable eggs
Give the summary of structural chromosomal aberrations
- Breakpoints are generally in non-coding areas
- In diploid organisms surplus of genetic material is better tolerated than the lack of it.
- Balanced carriers of chromosomal rearrangements are phenotypically normal
- Meiotic paring of rearranged chromosomes are often abnormal
- Balanced carriers have high risk to produce unbalanced offspring
- Chromosomal imbalance causes severe phenotypic abnormalities or death
(There are exceptions )
