Genetics: Single gene and chromosome abnormality Flashcards by Anna Hay

What is the meaning of haploid cells?

Haploid cells only contain 23 chromosomes, the germ cells.

All somatic cells have 46 chromosomes, the diploid number

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Describe what happens in meiosis 1

DNA duplication of chromosomes
Homologous chromosome recombinant with non identical chromatids (mixes maternal & paternal DNA)
Duplicated chromosomes then split to form 2 new daughter cells (with 2 x chromatids in each)

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Describe what happens in meiosis 2

Single chromosome split into sister chromatatids & pulled to side of cell before cytokinesis.

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How many daughter cells are made from one dividing germ cell during meiosis

4 - each containing 23 chromosomes

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What is the difference between the development of the germ cell between ovum and sperm after meiosis

Female: 3 daughter cells form polar bodies and will not survive, 1 becomes ovum
Men: All develop into spermatozoa

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What is the meaning of aneuploidy?

Abnormality of number of chromosomes

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What are the main mechanisms resulting in aneuploidy

Non-disjunction

Translocation

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How does nondisjunction occur?

Pairs of homologous chromosomes at meiosis 1 or sister chromatids during mitosis do not separate so both chromosomes are passed onto on daughter cell (trisomy), whilst one is left missing one chromosome (monosomy)

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Name some trisomy conditions

Downs syndrome 
Edwards Syndrome
Patau syndrome 
Klienfelter (XXY)
Triple X syndrome (XXX)
XXY syndrome (XXY)

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What % of does syndrome is caused by nondisjunction?

Other cause?

95%

Robertsonian Translocation

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What medical conditions are often present in those with Downs Syndrome?

Learning difficulty 100%
Cardiac problems atrioventricular defects (40-50%)
Hypothyroidism 20-40%
Dementia 10-15%
Acute Lymphoblastic anaemia

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What chromosome is trisomy in edwards syndrome?

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What are the clinical features of Edwards Syndrome?

Babies likely to die within 1 year
Profound learning difficulty 
Congential heart disease (90%, VSD)
Facial clefts
Spina bifida 
Clenched hands
Rockerbottom feet

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What chromosome does Patau syndrome effect?

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What are the clinical features of patau syndrome?

High rate miscarriage 
Profound learning difficulty
Congential heart disease 
Postaxial polydactyly 
Cleft palate
Microphthalmia

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Clinical features of klinefelter syndrome

Slightly descreased IQ
Tall stature
Infertility
Transient gynaecomastia

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Whats the risk of nondisjunction at 20 vs 40 yrs

20: 1 in1500
40: 1:100

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Name a monosomy resulting from nondisjunction

Turners syndrome 45X

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What are the clinical features of Turner syndrome?

Mildly Lower IQ
Many do not survive due to fetal hydrous
High risk of miscarriage
Consider NT >4mm

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What is the difference between balanced and unbalanced reciprocal translocation?

Chromosome rearrangement between 2 nonhomologus chromosomes.

Balance: No phenotypic consequence
Non balances: 1 chromosome with missing genetic material (monosomy) and 1 with duplicate genetic material (trisomy)

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If a parent with balanced translocation has children with partner with normal chromsomes what are the possible outcomes

25% normal chromsome
25% balanced translocation
50% unbalanced translocation → risk sport miscarriage or go to term with child with high risk learning difficulty etc

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Explain robertsionian translocations

Chromsome rearrangement that involves fusion of the long arms of 2 afrocentric chromosome and their short arms are lost.

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Which chromosomes can have robertsonian translocations?

13, 14, 15, 21 & 22

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13q, 14q and 14q,21q are the most common robertsoninan translocations, which conditions are these?

13q14q patau

14q 21q downs

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What is imprinting and which chromosomes are vulnerable?

One parent allele is preferentially silenced | 14&15

What conditions is paternal uniparental disomy (UPU15) | Some features?

Angelman syndrome characteristic face and ataxic fain severe learning difficulty

What conditions is maternal uniparental disomy (UPU15) | Some features?

Prader-willi poor feeders in neonatal period, insatiable appetite from childhood, hypotonic and short, learning difficulty

What technique is used to identify micro deletions or micro duplications?

aCGH

In micro deletions what mechanisms abrogate gene function:

``` missense mutation truncating mutation (frameshift, nonsense) Splice site partial gene deletion whole gene deletion triplet repeat expansion ```

What common conditions are from triplet repeat expansion?

Huntingdons, myotonic dystrophy, fragile x

Which micro deletion is williams syndrome

7q11

what are the features of williams syndrome

mild/severe learning Cardiac aortic/pulmonary stenosis renal artery stenosis cocktail party personality

which micro deletion if diGeorge

22q11

what are the features of diGeorge

``` Leanrind difficulty cardiac fallot, vid short cleft palate low calcium ```

4 ways genes can be inherited?

``` AD AR X linked r X linked d mitochondrial ```

Main features of tuberous sclerosis

AD multisystem, cutaneous (shagreen patches) neurological (brain hamartoma - seizure) prenatal: rhabdosacroma

Main features of neurofibromatosis type 1

AD Cafe-au-let spots neurofibromatoma inguinal freckling and optic glioma

Main features of HNPCC

AD | cancer: colon, endometrium, gastric and ovarian

Main polycystic kidney disease

AD Cysts in the kidney, liver, pancreas & spleen CV abnormality intracranial anrueysm mitral valve prolapse

Main features of haemochromatosis

AR | excess iron absorption in liver, pancreas and skin (cirrhosis, DM, bronze skin)

Main features of alpha 1 antitrypsin

AR | no elastase, emphysema at young age and cirrhosis

congenital adnreal hyperplasia (21 hydroxyls deficiency)

AR Unable to synthesis cortisol female virilisation precocious puberty +/- salt wasting

Main features of duchenne muscular dystrophy

X linked R | Progressive myopathy. death in 3rd decade resp failure

Main features of Haemophilia A

X linked R | Deficiency factor VIII, abnormal clotting

Main features of Fragile X syndrome

X linked R Expansion of CGG Learning difficulty and appearance

What is the likely outcome for a male fetus that inherits an X linked dominant condition

spent loss of pregnancy | early neonatal death

Main features of Rett Syndrome

Cognitive regression and learning difficulty | hand wringing, sterotypical movement

At what weeks can't the nuchal translucency be tested?

11-14 weeks

What other findings other than nuchal translucency in 1st trimester are associated with trisomy 21

Absent or hypoplastic nasall bone | Absant or reversed A wave in blood flow of ductus arterisosis

What is included in the triple test? | How accurate is it for detecting trisomy 21

NT, bHCG and PAPPA | 90%

Positive finding of triple test?

High NT high bHCG low PAPPA

What tests are perfromed in the triple screen

aFP bHCG Estriol 70%

Findings of triple test in Downs

afp & estriol low | bHCG high

finding triple test in edwards

all low

high alpha fetoprotein is associated with what?

Neural tube defects

What tests are in the quadruple test? Accuracy

``` aFP bHCG Estriol Inhabin 81% ```

when is triple test/quadruple test performed

16-18 weeks

What is cell-free fetal DNA testing? What is it tested for?

Non invasive, small amount fetal DNA used to determine gender, rhesus status + trisomy 13,18,21

When can CVS happen? | What is aspirated?

11 weeks-14weeks | Placental tissue

What is the difference in sampling cytotrophoblast vs mesenchymal cells during CVS?

Cytotrophoblasts are rapidly dividing, results in 2-3 days | mesenchymal cells 1-3 weeks but more accurate

Risk of false positive in CVS & why

1.5% Placental mosaicism, present in placenta but not fetal tissue

When is amniocentesis performed? When cells are tested? How long for result & why?

15 weeks Amniocytes (in amniotic fluid), fetal skin, urinary tract & GI tract 1-3 weeks - no rapidly dividing cells.

Miscarriage rate of amniocentesis and CVS

When can cordcentbesis be performed? | What can is test for?

From 18 weeks anaemia, prenatal infection 1-2% misc rate

Which molecular genetic techniques measure gene dosage at particular locations in the genome?

FISH (Fluorescence in situ hybridisation) QF PCR (Quantative fluorescence polymerase chain reaction) MLPA (Multiplex ligation probe aplification)

Which molecular genetic techniques measure gene dosage over the entire genome? What is the benefit of this over the other methods mentioned?

aCGH (microarray comparative genetic hybriddisation) Can also detect micro deletions or micro duplications as we'll as aneuploidy

What is the lifetime risk of developing ovarian cancer in the general population? What % is due to BRCA1&2 genes?

1 in 70 | 6-8%

Lifetime risk BRCA1 in developing breast & ovarian cancer?

Breast 60-90% | Ovarian 40-60%

Lifetime risk BRCA2 in developing breast & ovarian cancer?

Breast 45-85% | Ovarian 10-30%

What % of overall breast cancers are due to BRCA1&2

In HNPCC lifetime risk of endometrial cancer risk?

50%

In Peutz-Jegher syndrome, what is the lifetime risk of endometrial cancer?

40% 30% bowel cancer - pigmented macules in mucus membranes and skin + GI

Genetics: Single gene and chromosome abnormality Flashcards

(72 cards)