Q2-FUN17/Cytogenetics (human chromosomes and chromosomal disorders) Flashcards by Adarsh Aratikatla

What is the leading indication of a pre-natal of a potential disease?

mother is older

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The lab methods for pre-and post natal diagnosis are similar, but they have different ____________ methods

sampling

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Typically, we start with ________ methods and then to confirm the diagnosis, we move to _______ clinical procedures

non-invasive, invasive

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What are the 2 types of prenatal invasive methods?

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What is chorionic villus sampling?

it is a prenatal, invasinve test where a sample of chorionic villi is removed from the placenta for testing

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What is amniocentesis?

prenatal invasive procedure used to take out a small sample of the amniotic fluid for testing

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invasive procedures incur ________

risk!

Doctors have to ask themselves if the risk of procedure is greater than the risk of fetal abnormality?

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noninvasive prenatal diagnosis is relevant to screening for __________

down syndrome

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What are the non invasive tests done during the first trimester of pregnancy?

Maternal serum proteins + ultrasound (subcutaneous edema of fetal neck)

– PAPP-A (pregnancy associated plasma protein A)

– fβHCG (free-beta human chorionic gonadotropin)

– Maternal Serum α-fetoprotein,

– hCG,

– unconjugated estriol

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What is the Harmony test?

it is a non-invasive prenatal tests (NIPT), it analyses cell-free DNA (cfDNA) in maternal blood plasma.

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Why does the harmoney test work?

It works because blood plasma of a pregnany woman consists of a combination of both maternal (95%) and fetal (5%) DNA.

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What advancements have occured regarding the Harmony test since 2012?

it is now possible to analyse cell free fetal DNA (cffDNA) in the maternal blood using Next Generation Sequencing (NGS)

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What does the harmony test look for?

gives a strong indication of whether the baby is at high or low chance of having trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) or trisomy 13 (Patau syndrome).

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CVS is a biopsy of the villi in the _____________ via a __________ under _________ guidance

chorion frondosum, catheter, ultrasound

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What are the advantages of CVS?

It happens in the first trimester

yields 10-50mg of tissue for quick analysis

tissue culture isnt nessessary to inc. cell numbers

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What are the disadvantages of CVS?

no a-fetoprotein for diagnosing NTD (neural tube defect)

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What is the risk of miscarriage for CVS?

1% above 2-5% baseline

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Is the risk of miscarriage greater for CVS or amniocentesis?

CVS

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Amniocentesis is the withdrawl of amniotic fluid (____-____ ml) under _____ guidance

10-20 ml, ultrasound

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CVS occurs trans______ or trans_______

transcervically or transabdominally

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Amniocentesis occurs trans_________

transabdominally

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When would someone perform an amniocentesis?

early second trimester (15-20 weeks)

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Since amniocentesis collects fluid and that amniotic fluid contains cells, it can be ___________

cultured

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what can be measured from amniotic fluid?

alpha-fetoprotein, used to test for neural tube defects

can also find enzymes and viruses

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how long do you have to culture cells that you got from amniocentesis for?

culture them from 4-6 weeks, most are nonviable cells

what is the risk of miscarriage of amniocentesis?

approx. 0.2% above the baseline 1-2%

What are the differences between metacentric, submetacentric, and acrocentric?

where the centromere is located

Explain banding nomenclature for chromosomes.

What are the 2 types of chromosomal abnormalities?

numberical aberrations and structural aberrations

What is a numerical chromosome aberration?

Numerical abnormalities are _whole chromosomes either missing from or extra_ to the normal pair.

What are the 2 types of strutural aberrations?

involving 1 chromosome and involving 2 chromosomes

What are the types of structural aberrations involving 1 chromosome?

duplication, deletion, inversion, ring chromosome

What are the types of structural aberrations involving 2 chromosomes?

reciprocal translocations and robertsonian translocations

What is a robertsonian translocation?

A Robertsonian translocation is one in which, effectively, the whole of a chromosome is joined end to end with another. This type of translocation involves only chromosomes 13, 14, 15, 21 and 22.

What is a reciprocal translocation?

Reciprocal translocation is a form of gene rearrangement where portions of two chromosomes are simply exchanged with no net loss of genetic information.

Aneuploidy arises from \_\_\_\_\_\_\_\_\_\_\_\_\_\_

chromosomal non-disjunction

What is a chromosomal non-disjunction?

it is the failure of homologous chromosomes to separate and segregate normally in either mitosis and meiosis

What happens when chromosomal non-junction occurs in meiosis?

Non-disjunction results in imbalanced gametes. If one of those gametes get fertilized, all of the cells that come from the resulting embryo will have a chromosome imbalance.

What happens when chromosomal non-junction occurs in mitosis?

Non-disjunction produces two cell-lineages derived from a single zygote (known as ‘Mosaicism’)

What is mosaicism?

Mosaicism occurs when a person has two or more genetically different sets of cells in his or her body.

Individuals who are mosaic for a particular chromosomal aberration usually have _____________ than those who are non-mosaic

less severe symptoms

Mosaicism occurs when non-disjunction happens during a \_\_\_\_\_\_\_\_\_\_\_\_\_\_

mitotic cell devision

Explain meiotic non disjunction.

When are the 2 times nondisjunction can occur in meiosis?

first and second meiotic division

What happens when non disjunction occurs in the first meiotic division?

gametes contain either _both_ parental chromosomes which didnt separate, or _neither_

What happens when non disjunction occurs in the second meiotic division?

gametes contain _2 identical copies of the same chromosome, or neither_

What are some clinical features of down syndrome?

Developmental delay Variable intellectual disability Characteristic facial features Congenital heart defects Premature ageing Risk of leukaemia

What are the 2 main causes of Down syndrome and their respective percentage chance of causing Down syndrome?

Trisomy 21 (95%) and Robertsonian translocation (5%)

What is the incidence of trisomy 21?

1/650 live births

The risk of trisomy 21 increases with maternal \_\_\_\_\_

age

What are some physical characteristics of someone with edwards syndrome?

rocker bottom feet, death usually within 1 year

What are some physical characteristics of someone with Patau syndrome?

polydactyly, death usually within 1 year

What are some physical characteristics of someone with Turner syndrome?

short stature, low set eyes

What are the 2 types of structural chromosome abnormalities?

unbalanced and balanced

Explain an unbalanced structural chromosome abnormality?

An unbalanced abnormality involves loss or gain of genetic material. Individuals with unbalanced abnormalities usually have developmental delay or congenital malformations.

Explain a balanced structural chromosome abnormality?

Balanced abnormalities do not have gain or loss of genetic material, but heterozygous individuals could be at risk for passing on the abnormality to offspring in an unbalanced form.

What are the various outcomes of gametes for a robertsonian translocation?

What are some clinical indications for prenatal cytogenetics?

1. Abnormal ultrasound 2. Advanced maternal age/biochemical test 3. Previous birth of child with trisomy 4. Infertility, recurrent spontaneous abortion 5. Carrier of heritable chromosome abnormality

What are some clinical indications for postnatal cytogenetics?

1. Dysmorphic features, congenital malformations 2. Developmental delay 3. Clinical features of specific chromosomal syndrome, e.g. Turners, Downs, Edwards etc.

What are microdeletion syndromes?

microdeletion syndromes involve deletions that are too small to be detected by G banding

microdeletion syndromes require _______ for diagnosis

molecular cytogenetic methods

each microdeletion syndrome has a pattern of ____________ that leads the clincian to query a particular syndrome

_different_ malformations

Since microdeletions are too small to be detected by G-band cytogenetics, what type of test do we use to find microdeletions?

fluorescence in situ hydridization (FISH)

What does imprinting mean?

there is a different expression of the same chromosomal region, depending on whether the region came from the mother versus father.

What is the difference between prader willi and angelman syndrome?

Prader Willi syndrome: deletion occurs on paternal chr 15 Angelman syndrome: deletion occurs on maternal chr 15 For PWS only 15q11 genetic material from mother is present For AS only 15q11 genetic material from father is present

What is an Array CGH?

it detects a very subtle gain or less of genetic material, it is much more sensitive than G-banded karyotyping

Array CHG has the same resolution as \_\_\_\_\_\_\_, but it uses a ___________ method

FISH, genome-wide detection

Array CGH should be used for all cases of ..............

unexplained developmental delay/intellectual disability autism spectrum disorders multiple congenital anomalies

What is the abnormality detection rate for Array CGH and G-banded Karyotyping respectively?

15%-20% - Array 3%- G band karyotyping

Array CGH is more/less expensive than G-band karyotyping