Cytogenetics

Question 1

THE HUMAN GENOME

•___ genes

___ chromosomes

___ pairs
•1-22 =
•23 =

Answer 1

•~20,000 genes
•
•46 chromosomes
•
•23 pairs
•1-22 = autosomes
•23 = sex chromosomes
•

Question 2

CHROMOSOME MORPHOLOGY

• •Centromere
  
  • •where ____ attaches to ___ ____during cell division
• •Telomere
  
  • •caps the ends of chromosomes, consists of___ ____
• •Chromosome Arms
  
  • •p (petit) = ___ arm, ___ centromere
  • •q = ___ arm, ___ centromere
• Metacentric:
• Submetacentric:
• Acrocentric:

Answer 2

• Centromere
• where chromosome attaches to spindle apparatus during cell division
• Telomere
• caps the ends of chromosomes, consists of repetitive sequences
• Chromosome Arms
• p (petit) = short arm, above centromere
• q = long arm, below centromere

Metacentric: centromere is center (1,2)
Submetacentric: Slightly to one side with distinct p and q arm (5)
Acrocentric: p arm is very small and doesn’t have many genes (13 14 15 21 22)

Question 3

CHROMOSOME MORPHOLOGY

•Acrocentric chromosomes
which ones? ___________

• Have___ and ___ composed of ___ ___
• Short arm/stalk/satellite region is common area of ____ ____

Answer 3

•Acrocentric chromosomes
•
•13, 14, 15, 21 & 22
•
•Have satellites and stalks composed of repetitive DNA
•
•Short arm/stalk/satellite region is common area of chromosome breakage

Question 4

KARYOTYPING

1

2

3

4

5

Answer 4

•
•Culture cells
•
•Stop mitosis in metaphase
•
•Fix chromosomes
•
•Stain
•
•View under microscope

Question 5

MEIOSIS

____ rounds of cell division
•
•Result is ____ cells

•

Answer 5

•
•
•2 rounds of cell division
•
•Result is haploid

cells

•

Question 6

NONDISJUNCTION

___ of two __ ___or ___ ___ to ___ leading to ____
•Can occur in____ or ____

Results in ____ gametes and____gametes

Answer 6

•Failure of two homologous chromosomes or two sister chromatids to separate leading to imbalance
•Can occur in meiosis I or meiosis II
disomic gametes and nullsomic gametes

Question 8

1 - POLYPLOIDY

___ ____ of chromosomes
•
_____: (3 copies of ___ ____)

Beyond triploidy,

Answer 8

•Multiple sets of chromosomes
•
•Triploidy (3 copies of each chromosome)
Beyond triploidy, even more incompatible with life, dont make it farenough for us to test for it

Question 9

TRIPLOIDY

___ anomalies
•
•Severe___ ___ ___
•
•Typically ___ (____% of all miscarriages)
•
____ placenta (diandric) or ___ placenta (digynic)

Incompatible with life

Miscarry very early

Answer 9

•Multiple anomalies
•
•Severe intrauterine growth deficiency
•
•Typically miscarry (1-3% of all miscarriages)
•
•Large placenta (diandric) or small placenta (digynic)

Incompatible with life

Miscarry very early

Question 10

2 - ANEUPLOIDY

•Deviation from an ___ ___ of the ____ number of chromosomes
•
_____ (__ copy of a chromosome)
•
_____ (__ copies of a chromosome)
•
_______ (__ copies of a chromosome)

Answer 10

•Deviation from an exact multiple of the haploid number of chromosomes
•
•Monosomies (1 copy of a chromosome)
•
•Trisomies (3 copies of a chromosome)
•
•Tetrasomies (4 copies of a chromosome)

Question 11

TRISOMY 21

Answer 11

•Dysmorphic
•
•Intellectual disability
•
•Hypotonia
•
•Heart defects
•
•Duodenal atresia
•
•Short stature

Question 12

TRISOMY 18

Answer 12

•Intrauterine growth deficiency
•
•Heart defect
•
•Kidney abnormalities
•
•Esophageal atresia
•
•Diaphragmatic hernia
•
•Omphalocele
•
•Profound intellectual disability
•
•Microcephaly:
•

Question 13

TRISOMY 13

Question 14

KLINEFELTER SYNDROME (XXY)

Question 15

TURNER SYNDROME (MONOSOMY X; XO)

Answer 15

•Lymphedema, webbing
•
•Short stature
•
•Heart defect (coarctation of the aortaà narrowing)
•
•Premature ovarian failure/infertility
•
•Developmental delay, nonverbal learning disabilities, behavioral problems

Question 17

PRENATAL SCREENING

1st trimester and 2nd trimester (___ screening) look at ___ and ___. An ___ ____can be associated with a___ ____ Not diagnositc

NIPT:___ ___ ___ ____: looks at ___ ___ ___ DNA produced by____ and then gets into ____ blood sstream. Still not looking at DNA directly from baby. Still not diagnostic

Answer 17

1st trimester and 2nd trimester (quad screening) look at hormones and proteins. An abnormal patter can be associated with a csome abnormality. Not diagnositc

NIPT: Non-invasive Prenatal Testing: looks at cell free fetal DNA produced by placental and then gets into maternal blood sstream. Still not looking at DNA directly from baby. Still not diagnostic

Question 18

INVASIVE PRENATAL TESTING

_____
•CVS (chorionic villus sampling): _____
•Samples the___ Still not testing baby directly
•Transabdominal or transcervical
•Risk for maternal contamination and placental mosaicism: ~___
•Risk for miscarriage: ______
•
•Amniocentesis: ____
•Samples the ____ ___
•Transabdominal
•Risk for maternal contamination: ____
•Risk for miscarriage: ________

•___, ___, ____ ___., ____ ____, ___ ____

Answer 18

DIAGNOSTIC!!
•CVS (chorionic villus sampling): 10-14 weeks
•Samples the placenta. Still not testing baby directly
•Transabdominal or transcervical
•Risk for maternal contamination and placental mosaicism: ~1%
•Risk for miscarriage: 1/150 - 1/250
•
•Amniocentesis: 15 weeks +
•Samples the amniotic fluid
•Transabdominal
•Risk for maternal contamination: ~0.1%
•Risk for miscarriage: 1/400 - 1/500

•Karyotype, CMA, gene sequencing, mutation analysis, biochemical testing*

Question 19

3 - MOSAICISM

• Presence of ___ than __ ___ __ in an ____
• Hard to predict ____ because l___ of ____ in ___ ___e cannot be determined

Mutation or nondisjcn orccured at some point. We can test levels of mosaicism in each tissue so we don’t know if cells with more normal are milder.

Can be___ in origin. All cells were normal, something happens to a few cells when fetus developing

Can be ____ in origin. Originally abnormal. Some cells tried to rescue themselves and kick out extra csome.

Answer 19

•Presence of more than one cell line in an individual
•
•Hard to predict prognosis because level of mosaicism in each tissue cannot be determined

Mutation or nondisjcn orccured at some point. We can test levels of mosaicism in each tissue so we don’t know if cells with more normal are milder.

Can be somatic in origin. All cells were normal, something happens to a few cells when fetus developing

Can be meiotic in origin. Originally abnormal. Some cells tried to rescue themselves and kick out extra csome.

Question 20

4 – UNIPARENTAL DISOMY

•___ copies of a chromosome (or ___of a chromosome) inherited from the ___ parent
___ copies are inherited from the other parent
•important for ____ genes
•

•Types
•Heterodisomy: Nondisjcn in meiosis _(two copies are ____)
•Isodisomy: Nondisjcn in meiosis ___ (two copies are ____)
•
•Methods
•
•
•

Answer 20

•2 copies of a chromosome (or part of a chromosome) inherited from the same parent
•
•no copies are inherited from the other parent
•
•important for imprinted genes
•

•Types
•Heterodisomy: Nondisjcn in meiosis I (two copies are different)
•Isodisomy: Nondisjcn in meiosis II (two copies are identical)
•
•Methods
•Trisomy rescue
•Monosomy rescue
•+/- Unequal crossing over

Question 21

PRADER-WILLI SYNDROME

Answer 21

•Hypotonia
•
•Mild intellectual disability
•
•Behavioral problems (temper tantrums, manipulative, OCD)
•
•Insatiable appetite àobesityàdiabetes
•
•Hypogonadism
•
•Almond-shaped eyes
•
•Maternal UPD 15 (paternal copy is missing)

Question 22

Microdeletions/ duplications

___ or ____ of a ___ ___, not an entire chromosome

Answer 22

•Deletion or duplication of a chromosomal region, not an entire chromosome

Question 23

WOLF-HIRSCHORN SYNDROME

Answer 23

•“Greek warrior helmet” appearanceà wide nasal bridge, widge eyes
•
•Intellectual disability
•
•Cleft lip and/or palate with dental abnormalities (missing or extra teeth within cleft)
•
•Seizures
•
•Microcephaly
•
•Hypotonia

Question 24

22q11.2 DELETION SYNDROME

____
____

___ ____

Answer 24

aka DiGeorge, Shprintzen and velocardiofacial syndromes

Question 25

FISH

•FISH = ___ ___ ___ ____
•Uses___ ___s that are ____ to a __ ___ ___
•
•Detects ___ ___ and ____

Used for

__________

Have to ________

Answer 25

•FISH = Fluorescence in situ hybridization
•
•Uses DNA probes that are specific to a targeted chromosomal region
•
•Detects targeted deletions and duplications

Used for things too small to see on karyotype

On its way out

Have to know exactly what you testing for

Question 26

CHROMOSOMAL MICROARRAY

_____ of DNA probes across the genome, on each chromosome, are used to detect___ and ____
•Can detect ________ ____ and ____ than karyotyping and does ___ ___ a ___ , ___ region like FISH

Probes across all DNA on all csomes

not picking up enough signal: ____

too much signal_____

This is what we use now to test for ___ ____

Answer 26

• Thousands of DNA probes across the genome, on each chromosome, are used to detect deletions and duplications
• Can detect smaller del/dups than karyotyping and does not require a known, targeted region like FISH

Probes across all DNA on all csomes

not picking up enough signal: deletion

too much signal: duplication

This is what we use now to test for csomal abnormalities

Question 27

TRANSLOCATIONS

____ of chromosomal material

•Balanced:
All genetic material is ___, just ____ onto diff csome
Robertsonian- occurs in the ___ ____chromosomes (__ __ __ __ __)

Unbalanced
____ and/or ____ of chromosomal material in ____ form

Answer 27

•Rearrangement of chromosomal material

•Balanced:
All genetic material is present, just rearranged onto diff csome
Robertsonian- occurs in the 5 acrocentric chromosomes (13, 14, 15, 21, 22)

Unbalanced
Loss and/or gain of chromosomal material in rearranged form

Question 28

BALANCED TRANSLOCATION

•Typically _______________on health unless an important gene is interrupted at the_____

Problem is when___ have ___–> ____

Answer 28

•Typically does not have impact on health unless an important gene is interrupted at the breakpoint

Problem is when they have kids–> unbalanced

Question 29

UNBALANCED TRANSLOCATION

____ ___ of some chromosomal information and ___ ___of other (___ ___ and ___ ___)

Any time you see extra and missing in a karyotype: ask if _________________

Answer 29

•
•Too much of some chromosomal information and too little of other (partial trisomy and partial monosomy)

Any time you see extra and missing in a karyotype: ask if parent has balanced translocation

Question 30

ROBERTSONIAN TRANSLOCATION

___ ____ csomes ___ to form ___ csome

Answer 30

•2 acrocentric chromosomes (13, 14, 15, 21, 22) fuse to form 1 chromosome

Question 31

REPRODUCTIVE RISKS

Balanced translocation carrier can pass on____ ____ (______), ___ ___ of translocation (kid ___ ___) or ___ copy of translocation (___ ___).

***** If a parent has a ___ ____ between the __ ____(i.e. 21;21) ____of the offspring will have a ___ _____*****

Answer 31

Balanced translocation carrier can pass on normal copies (kid normal), both copies of translocation (kid translocation carrier) or one copy of translocation (kid unbalanced).

***** If a parent has a Robertsonian translocation between the same chromosomes (i.e. 21;21) 100% of the offspring will have a chromosomal abnormality*****

Question 32

INVERSIONS

Answer 32

•
•Paracentric = no centromere involvement
•
•Pericentric = centromere involvement

Question 33

REPRODUCTIVE RISKS

Question 34

SUMMARY

Answer 34

•
•Abnormalities of chromosome number and structure can cause genetic syndromes
•
•Some chromosome abnormalities can be inherited (i.e. inversions and translocations) while others occur sporadically during cell division (i.e. trisomy and mosaicism)
•
•Genetic testing to identify these chromosomal abnormalities includes karyotyping, FISH and chromosomal microarray analysis