PAX, SOX, POU and Zn Finger Genes Flashcards
What PAX genes are in Group I
PAX 1 and 9
What PAX genes are in Group 2
PAX 2, 5 and 8
What PAX genes are in Group 3
PAX 3 and 7
What PAX genes are in Group 4
PAX 4 and 6
What does a mutation in PAX 1 Cause
Curved ‘undulated’ spine in mice
What does a mutation in PAX9 cause
Oligodontia in humans
Missense mutations
Lack of 6 teeth
What does a mutation in PAX2 cause
Renal Colomba Syndrome
Involves optic nerve tumours, kidney and ear defects
What does a mutation in PAX8 cause
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
What does a mutation in PAX5 cause
Large cell lymphomas (non-Hodgkins)
t(9:14) puts PAX5 next to the adjacent IG heavy gene that is highly expressed
What does a germline mutation in PAX3 cause
PAX3 is required for embryonic migration and neural crest cells
Mice = splotch mutation = abnormalities of pigmentation and NTDs Human = Waardenurg Syndrome = hypopigmentation and deafness
What does a somatic mutation in PAX3 cause
Alveolar rhabdomyosarcoma
t(2:13) forms a PAX3-FKHR fusion protein –> an oncogenic transcription factors
What does a somatic mutation in PAX7 create
Alveolar rhabdomyosarcome
t(1;13) produces a similar PAX7-FKHR fusion protein –> but slightly better outcome than for PAX3
What does PAX6 mutations cause in humans
WAGR Wilms Tumour Aniridia Genitourinary Defects Retardation
Pax 6 also thoguht to be the ye gene
4 type of Zn finger genes
TFIIIA
Nuclear Hormone receptors
Retroviral GAG Products
Yeast Transcription Factors
Make up of TFIIIA subclass of Zn finger genes
CC/HH
Make up of nuclear hormone receptor subclass of Zn finger genes
CC/CC
Make up of retroviral GAG products subclass of Zn finger genes
CC/HC
Make up of Yeast trasncription factors subclass of Zn finger genes
6xC
What does mutations in Gli3 Zn finger gene cause
Mice = extra troes Humans = Greigs syndrome: skeletal malformations of hands, feet and cranium
What do mutation in WT1 Zn finger genes cause
WAGR and Drash Syndrome
WT1 is on the same part of chromosome 11 as PAX6 so deletion cgets rid of both of them!
What does POU5F1 encode
Oct4
What does POU1F1 encode
PITI protein –> deficiency causes combined pituitary hormone deficiency
What groups of PAX genes are bad prognosis
II and III
Roles of PAX 3 and 7
Role in stem cell self renewal
Also required for the proper migration and specification of progenitor cells in embyrogenesis neural-crest derived cells
What PAX gene is overexpressed in melanomas
PAX3
PAX3 also contains a 9th exon PAX9d in these tumours but its importance is not yet known
Mechanism of the PAX-3/7 fusion proteins
May increase MET tyrosine kinase receptor –> Activates it –> Activates STAT 3 –> acquires invasive behaviour
What are PAX 2 and 8 important for
Stem cell survival and lineage commitment in development
What is PAX5 important for
B cell deevleopment
Which PAX gene expresses anti-tumorigenic activity
PAX6
Increased PAX6 in malignnat astrocyte gliomas conveyed a good prognosis
Which PAX gene may infleunce p53
PAX5 though it may directly inhibit p53 hence leading to tumour cell survival
Give an example of SOX genes controlling stepwise development
In Melanocytes
First SOX10 - with PAX3 promote MitF TF
Then MitF and SOX10 promotes Oct and Tyr genes involved in melanocyte development
Give an example of SOX working with a partner genes
SOX2 and Oct4 enhances FGF4!!!
What is the SOX2 and OCt4 complex important for
Essential for the formation of the inner cell mass in the preimplantation embryo
