autosomal recessive disease and reproduction Flashcards

1
Q

Where are all recessive condition mutations located on a chromsome

A

Between 1-22 on chromosome = autosomes

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2
Q

What is compund heterozygous vs recessive

A

Compund heterozygous - both alleles contain a different variant affected by recessive condtioon
Recessive = 2 copies of same gene with same mutation on that chromosome

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3
Q

incidence of CF in the UK

A

1 in 2500

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4
Q

What causes cystic fibrosis

A

CFTR gene mutation on chromsome 7 , most commonly delta 508 mutation
Cystic fibrosis transmembrane conductance regulator = cell mebrane chloride transporter

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5
Q

What is tay sachs disease

A

HEXA gene mutation codes for enzyme that breaks down toxic CNS products - severe neurodegnerative condition

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6
Q

What chances do a carrier coupleof having diseased children (each has one faulty copy) recessive disease

A

1 in 4 unaffected entirely or affected child
1 in 2 carrier

Of the unaffected children 2 in 3 are carrers

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7
Q

What are the outcomes of pregnancy for affected and unaffected partner recessive disease

A

All offspring will be carriers
if other parent is carrier offspring - 1in 2 chance of affected childrne
Direct children otherwise not affected unless chromsome deletions etc

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8
Q

Features of autosomal recessive pedigrees

A

Horiozontal pattern - siblings affected
Cant always follow disease through pedigree (usually not one generation after the oterh)
Parents and children of afected individuals usually unaffected
Males and females affected equally
More likely in consaguineous pedigrees or closed populations

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9
Q

What is consanguinity

A

Having children with relations second cousin or closer
ASK FH

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10
Q

How is consagnuinity shown on pedigree

A

Double horizontal line between couple

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11
Q

How is carrier testing offered

A

If someone found to be a carrier, offer testing to first degree relatives and partners
Find out chance of having affected child
Specifically test for idetifited mutation
Not done in children

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12
Q

How calculate risk calculation of passing on autosomal recessive disease

A

3 things - father and mother must be a carrier, both must pass on mutation - 1 in4

Chance of mum being a carrier x chance of dad being a carrier x 0.25

eg population chance of being a carrier or known carrier status = 1

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13
Q

What aware about when testing recessive disorders in partners of carriers

A

90% of CFTR mutations tested for - reduces risk significantly but could have rarer mutation
Consider different ethnic groups who may have different genetic mutations

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14
Q

What is pre implantation genetic diagnosis

A

Assisted production eg IVF/ICSI embryo biopsy taken from day 5-7
Testsing by FISH analysis, SNP array or test for known mutation in single gene disorder

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15
Q

What need to meet for PGD crtieria

A

Like IVF
Age, health, already have child?, couples relationship eg living together

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16
Q

Chorionic villous sampling - look at paeds!!

A

Sampling of cells taken from chorion between 11 -14 weeks

17
Q

Why can results be uncertain from chorionic villous sampling

A

Placental mosaicism - mutation may onyl be in cells of placenta, not embryo

18
Q

What is amniocentesis

A

Foetal cells in amnitoic fluid smapled at 15 weeks gestation
Can cause oligohydraminos and miiscarriage

19
Q

Chance of miscarriage in chroionic villous smapling vs amniocentesis

A

0.5% amniocentesis at 15 weeks
1% CVS at 11-14 weeks

20
Q

What is non invasice prenatal testing (screening) /diagnosis (for sepcific mutatuon)

A

Aneuploidy screening - analysis of cell-free DNA (cffDNA) in maternal bloodstream
NEPT - non invasing Testing
NIPD - non inveasive [reantal daignosis

21
Q

When can you do prenatal non invasive testing

A

Only sufficient for analysis from 10 weeks
present from 4 weeks in blood but not enough to analyse

22
Q

Who is offered X linked testing on NHS

A

X linked disorders
Disorders w gender specific phenotypes eg congenital adrenal hyperplasia

23
Q

Ecamples of x linked disorders that can mean sex tested for

A

Duchennes musuclar dystrophy- severe in boys, female carriers normally unaffected

24
Q

Congenital adrenal hyperplasia why can test for sex with this condition

A

Ambigious genitalia in females and severe salt wasting neonatally
Can improve outcomes in pregnancy with materanl dexamethasone which is why tested for

25
How test for sex of baby with NIPD
Maternal serum sample Test for Y chromsome specific DNA sequences - absent = female, present = male
26
What can NIPD be used for
Sex testing Specific mutation in singel gene disorder
27
Where is NIPD useful in single genetic disorder testing
De novo muation identified in prev preganncy or affected chid Paternal mutation in dominant disorder Known patenral mutation in recessive condition where both parents care carriers Extremely low cahnce affected if not detected Higher if it is detected
28
How is NIPT used in aneuploidy testing
Sinlge molecule DNA counting See more DNA in a chromosome -> trisomy Need to confirm with invasice testing before diagnosis
29
Maternal factors affecting NIPD/T
Some women have v low foetal DNA fractions eg overweight, gestational age - less likely pick up Problem with DNA extraction/amplification Underlying chromosomal abnormality or tumour may affect results
30
Pregnancy factors affecting NIPD/T
Twin pregnancies Resolving second gestational sac Placental mosaicism
31
When test cord blood for genetic condition
Implications for management or care during childhood Otherwise no genetic testing needed
32
What is DYPD testing
Prescribed flurouracil-based chemotherapy considered need to do this test DYPD deficiency of enzyme -> severe toxicity to drugs eg 5-fluorouracil