PAX, SOX, POU and Zn Finger Genes

Question 1

What PAX genes are in Group I

Answer 1

PAX 1 and 9

Question 2

What PAX genes are in Group 2

Answer 2

PAX 2, 5 and 8

Question 3

What PAX genes are in Group 3

Answer 3

PAX 3 and 7

Question 4

What PAX genes are in Group 4

Answer 4

PAX 4 and 6

Question 5

What does a mutation in PAX 1 Cause

Answer 5

Curved ‘undulated’ spine in mice

Question 6

What does a mutation in PAX9 cause

Answer 6

Oligodontia in humans
Missense mutations
Lack of 6 teeth

Question 7

What does a mutation in PAX2 cause

Answer 7

Renal Colomba Syndrome

Involves optic nerve tumours, kidney and ear defects

Question 8

What does a mutation in PAX8 cause

Answer 8

Follicular thyroid tumours

t(2:3) causes a PAX8-PPARgamma fusion protein to form which is an oncogenic fusion protein that you can test for

Question 9

What does a mutation in PAX5 cause

Answer 9

Large cell lymphomas (non-Hodgkins)

t(9:14) puts PAX5 next to the adjacent IG heavy gene that is highly expressed

Question 10

What does a germline mutation in PAX3 cause

Answer 10

PAX3 is required for embryonic migration and neural crest cells

Mice = splotch mutation = abnormalities of pigmentation and NTDs
Human = Waardenurg Syndrome = hypopigmentation and deafness

Question 11

What does a somatic mutation in PAX3 cause

Answer 11

Alveolar rhabdomyosarcoma

t(2:13) forms a PAX3-FKHR fusion protein –> an oncogenic transcription factors

Question 12

What does a somatic mutation in PAX7 create

Answer 12

Alveolar rhabdomyosarcome

t(1;13) produces a similar PAX7-FKHR fusion protein –> but slightly better outcome than for PAX3

Question 13

What does PAX6 mutations cause in humans

Answer 13

WAGR
Wilms Tumour
Aniridia
Genitourinary Defects
Retardation

Pax 6 also thoguht to be the ye gene

Question 14

4 type of Zn finger genes

Answer 14

TFIIIA
Nuclear Hormone receptors
Retroviral GAG Products
Yeast Transcription Factors

Question 15

Make up of TFIIIA subclass of Zn finger genes

Answer 15

CC/HH

Question 16

Make up of nuclear hormone receptor subclass of Zn finger genes

Answer 16

CC/CC

Question 17

Make up of retroviral GAG products subclass of Zn finger genes

Answer 17

CC/HC

Question 18

Make up of Yeast trasncription factors subclass of Zn finger genes

Answer 18

6xC

Question 19

What does mutations in Gli3 Zn finger gene cause

Answer 19

Mice = extra troes
Humans = Greigs syndrome: skeletal malformations of hands, feet and cranium

Question 20

What do mutation in WT1 Zn finger genes cause

Answer 20

WAGR and Drash Syndrome

WT1 is on the same part of chromosome 11 as PAX6 so deletion cgets rid of both of them!

Question 21

What does POU5F1 encode

Answer 21

Oct4

Question 22

What does POU1F1 encode

Answer 22

PITI protein –> deficiency causes combined pituitary hormone deficiency

Question 23

What groups of PAX genes are bad prognosis

Answer 23

II and III

Question 24

Roles of PAX 3 and 7

Answer 24

Role in stem cell self renewal

Also required for the proper migration and specification of progenitor cells in embyrogenesis neural-crest derived cells

Question 25

What PAX gene is overexpressed in melanomas

Answer 25

PAX3

PAX3 also contains a 9th exon PAX9d in these tumours but its importance is not yet known

Question 26

Mechanism of the PAX-3/7 fusion proteins

Answer 26

May increase MET tyrosine kinase receptor –> Activates it –> Activates STAT 3 –> acquires invasive behaviour

Question 27

What are PAX 2 and 8 important for

Answer 27

Stem cell survival and lineage commitment in development

Question 28

What is PAX5 important for

Answer 28

B cell deevleopment

Question 29

Which PAX gene expresses anti-tumorigenic activity

Answer 29

PAX6

Increased PAX6 in malignnat astrocyte gliomas conveyed a good prognosis

Question 30

Which PAX gene may infleunce p53

Answer 30

PAX5 though it may directly inhibit p53 hence leading to tumour cell survival

Question 31

Give an example of SOX genes controlling stepwise development

Answer 31

In Melanocytes
First SOX10 - with PAX3 promote MitF TF
Then MitF and SOX10 promotes Oct and Tyr genes involved in melanocyte development

Question 32

Give an example of SOX working with a partner genes

Answer 32

SOX2 and Oct4 enhances FGF4!!!

Question 33

What is the SOX2 and OCt4 complex important for

Answer 33

Essential for the formation of the inner cell mass in the preimplantation embryo