Gene Dosage and Genomic Imprinting

Question 1

What is bi-allelic expression?

Answer 1

Where both alleles are required to express the gene for there to be the right amount of protein

Question 2

What is aneuploidy?

Answer 2

an unbalanced set of chromosomes due to excess or deficiency of individual chromosomes

Question 3

What is polyploidy?

Answer 3

a whole additional set of extra chromosomes

Question 4

What is trisomy?

Answer 4

a third copy of one chromsome

Question 5

What is monosomy?

Answer 5

where one complete chromosome is missing

Question 6

Which types of trisomy can carry to term?

Answer 6

trisomy 13, 18 and 21 and XXY, XYY etc.

Question 7

Which types of monosomy can carry to term?

Answer 7

XO

Question 8

What are the features of trisomy 21?

Answer 8

intellectual disability, congenital heart disease, characteristic facial features, anomalies of gastrointestinal tract, increased risk of leukaemia, immune system defects, early onset alzheimer like dementia

Question 9

How many genes are on chromosome 21?

Answer 9

200

Question 10

What are the features of trisomy 18 (Edward’s syndrome)?

Answer 10

intellectual disability, overlapping fingers, club foot, heart defects - most often fatal before birth or a few months after birth

Question 11

When is bi-allelic expression not required?

Answer 11

if the gene has autosomal recessive inheritance

Question 12

What is haplo-insufficiency?

Answer 12

where a single copy of the gene is not sufficient to support normal cell function

Question 13

What is monoallelic gene expression?

Answer 13

where only one copy of the gene can be expressed for cell function and bi-allelic expression is problematic

Question 14

What are two examples of monoallelic gene expression?

Answer 14

X chromosome inactivation and genomic imprinting

Question 15

What is the mechanism of X inactivation?

Answer 15

the X chromosome that is to be inactivated expresses a non coding RNA called Xist which intiates a wave of hyperchromatin to silence that X choromsome

Question 16

Which X chromosome is inactivated?

Answer 16

random - results in mosaicism within tissues and between tissues

Question 17

What is a Barr body?

Answer 17

the inactivated X chromsome

Question 18

What is Turner syndrome?

Answer 18

XO - indicates that some genes still need to be expressed on the inactivated X chromosome because there is still a phenotype with an XO genotype - features are short stature, infertility, absence of secondary sexual development and impaired neurocognitive function

Question 19

When does X inactivation occur in development?

Answer 19

between the 8 and 100 cell stage

Question 20

What is genomic imprinting?

Answer 20

where some genes are expressed exclusively from a chomosome from the father and some genes are expressed exclusively from a chromosome from the mother - the DNA is equivalent in sequence but not in function. Genomic imprinting is the process whereby the parental origin of a particular gene is “marked” by a reversible epigeneticmechanism

Question 21

When does imprinting occur?

Answer 21

imprint are erased in gametogenesis and re-established in parental specific pattern in mature gametes

Question 22

How many imprinted genes have been identified?

Answer 22

100

Question 23

What is parthenogenesis and what is the result?

Answer 23

where all chromosomes came from mum - results in an ovarian teratoma

Question 24

What is androgenesis and what is the result?

Answer 24

where all chromosomes came from dad - results in a malignant choriocarcinoma

Question 25

Are imprinted genes all expressed the same way in all tissues?

Answer 25

no - e.g. IGF2 is imprinted in many tissues but shows bi-allelic expression in the brain, liver and chondrocytes

Question 26

What is the imprinted region of chromosome 11?

Answer 26

11p15.5

Question 27

What is the parental conflict hypothesis?

Answer 27

that maternally expressed genes limit fetal growth and paternally expressed genes promote fetal growth

Question 28

How many imprinting birth defects have been recognised?

Answer 28

9

Question 29

What are the four ways that imprinting disorders can occur?

Answer 29

deletions or duplications in sites of imprinted genes which results in loss of heterozygosity, uniparental disomy, alteration in epigentic markers (epimutation), mutation in imprinted genes or in imprinting control centres

Question 30

What is uniparental disomy?

Answer 30

Where both chromosomes have been inherited from one parent - can result in a lack of one type of genes and a duplication of the other type of genes

Question 31

What is the origin of UPD?

Answer 31

meiotic non dysjunction

Question 32

What is Beckwith-Wiedemann syndrome?

Answer 32

an imprinting disorder on chromosome 11 which results in macroglossia, overgrowth, abdominal wall defects, hypoglycaemia, risk of abdominal tumours

Question 33

When is there a greater risk of BWS?

Answer 33

in IVF

Question 34

What is Prader Willi syndrome?

Answer 34

a deficinecy of paternally expressed genes on chromosome 15 - results in hypotonia, hyperphagia, obesity, hypogonadism, small hands and feet, moderate intellectual disability

Question 35

What is Angelman syndrome?

Answer 35

a deficiency of maternally expressed genes on chromosome 15 - results in severe intellectual disability, absent speech, inappropriate laughter, repetitive ataxic movements, large mouth, protruding tongue, unusual seizures

Question 36

What is the inheritance of mutations in imprinted genes?

Answer 36

if the mutation is in active paternal genes then carrier males and affected males can have affected children but not carrier children, carrier females and affected females can have carrier children but not affected children. If the mutation is in active maternal genes then carrier females and affected females can have affected children but not carrier children and carrier males and affected males can have carrier children but not affected children