12-08-2006, 01:41 PM
HOX genes share a common domain which is the HOMEODOMAIN, as a result, the HOX genes are referred to as homeotic genes. There are 11 HOXA genes, and 9 HOXB, HOXC, and HOXD genes; or a total of 38 HOX genes - 39 HOX genes. The DNA sequence that codes the homeodomain is a highly conserved 180-base pair sequence termed the HOMEOBOX. The homeodomain is a helix-turn-helix structural motif that is common to DNA binding proteins, such as transcription factors.
HOX A1- inner ear malformations
(HOX A-1 overexpression- up regulation of bcl-2 (anti-apoptotic factor)
HOX A2: transformation of the pharyngeal arch 2 into the pharyngeal arch 1 with duplication of the malleus and the incus.
HOX B2: facial nerve palsy, motor nucleus deficiency of cranial nerve of pharyngeal arch 2
HOX A13 causes hand foot and genital syndrome: malformation of the thumb and great toe, bicornuate uterus, ectopic ureter openings and hypospadias.
Vertebral
Mutation of HOX C8 : A null mutation of HOX C-8 lead to transformation of the first lumbar vertebra into a 14th thoracic vertebra, and the eight rib became attached to the sternum.
Mutation of HOX 10 - no lumbar vertebrae are formed. Instead, ribs project from all posterior vertebrae, extending caudally from the last thoracic vertebrae to beyond the sacral region.
Mutation of HOX11 - sacral vertebrae are not formed and instead these vertebrae assume a lumbar identity
HOX-D 13 : is associated with synpolydactyly (fusion of fingers or toes)
SHH-Polydactyly
BMP-Syndactyly
Hox A-9 : AML
Hox-11 : T-cell ALL
PAX3 “ necessary for correct formation of caudal neural crest derivatives and migration of myoblasts into the limbs
Mutation causing loss of function- Waardenburg syndrome - a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes.
Mutation causing gain of function- Alveolar Rhabdomyosarcomas:-Fusion of PAX-3 with FKHR gene (another transcription factor)
PIT-1 “ -( Pituitary-specific transcription factor ) Mutation cause Combined Pit hormone deficiency
Pbx-1: Pre-B cell ALL
GBX and NKX 3.1: Prostrate CA
PAX 6 - aniridia in humans, misplaced eye in Drosophila
TCOF 1 - Treacher Collins syndrome
SOX 10 “ Hirschsprung disease
HOX A-9, 10, 11 - epithelial ovarian cancer
HOX B-5 congenital lung abnormality
Chapter 11: Development of the Limbs
1. An infant exhibits amelia (total absence of a limb). Findings of experimental studies in birds and mice are consistent with the possibility that the limb bud AER failed to express which of the following factors?
A. HOX gene transcription factor
B. Bone morphogenetic substance
C. LIM gene transcription factor
D. WNT gene factor
E. Fibroblast growth factor
2. Recent studies support the likelihood that syndactyly caused by failure of apoptosis between the digital rays may result from disruption of expression of which of the following factors?
A. Bone morphogenetic substance
B. Fibroblast growth factor
C. WNT gene factor
D. Insulin-like growth factor
E. LIM gene transcription factor
3. An infant is born with absence of the ulna and radius and malformations of the carpals and hand. Recent studies show that unique limb segment identities are encoded by HOX genes as follows (scapula - HOX9; humerus - HOX9HOX10; ulna,radius - HOX9HOX10HOX11; proximal carpals - HOX9HOX10HOX11HOX12; distal carpals, metacarpals, phalanges - HOX9HOX10HOX11HOX12HOX13). Therefore, disruption of expression of which of the the following HOX gene families would most likely account for this anomaly?
A. HOX9
B. HOX10
C. HOX11
D. HOX12
E. HOX13
4. An infant born with teratogen-induced phocomelia was probably subjected to which of the following teratogenic substances during the indicated sensitive period.
substance sensitive period
A.
B.
C.
D.
E.
alcohol
thalidomide
phenytoin
cadmium
retinoic acid
4-8 weeks
2-3 weeks
4-8 weeks
2-3 weeks
4-8 weeks
5. In cases of mirror polydactyly, which of the following factors, produced within the early limb bud, is both expressed by and restricted to the newly formed caudal orthotopic ZPA and the cranial ectopic ZPA?
A. BMP4
B. FGF4
C. SHH
D. IGF1
HOX A1- inner ear malformations
(HOX A-1 overexpression- up regulation of bcl-2 (anti-apoptotic factor)
HOX A2: transformation of the pharyngeal arch 2 into the pharyngeal arch 1 with duplication of the malleus and the incus.
HOX B2: facial nerve palsy, motor nucleus deficiency of cranial nerve of pharyngeal arch 2
HOX A13 causes hand foot and genital syndrome: malformation of the thumb and great toe, bicornuate uterus, ectopic ureter openings and hypospadias.
Vertebral
Mutation of HOX C8 : A null mutation of HOX C-8 lead to transformation of the first lumbar vertebra into a 14th thoracic vertebra, and the eight rib became attached to the sternum.
Mutation of HOX 10 - no lumbar vertebrae are formed. Instead, ribs project from all posterior vertebrae, extending caudally from the last thoracic vertebrae to beyond the sacral region.
Mutation of HOX11 - sacral vertebrae are not formed and instead these vertebrae assume a lumbar identity
HOX-D 13 : is associated with synpolydactyly (fusion of fingers or toes)
SHH-Polydactyly
BMP-Syndactyly
Hox A-9 : AML
Hox-11 : T-cell ALL
PAX3 “ necessary for correct formation of caudal neural crest derivatives and migration of myoblasts into the limbs
Mutation causing loss of function- Waardenburg syndrome - a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes.
Mutation causing gain of function- Alveolar Rhabdomyosarcomas:-Fusion of PAX-3 with FKHR gene (another transcription factor)
PIT-1 “ -( Pituitary-specific transcription factor ) Mutation cause Combined Pit hormone deficiency
Pbx-1: Pre-B cell ALL
GBX and NKX 3.1: Prostrate CA
PAX 6 - aniridia in humans, misplaced eye in Drosophila
TCOF 1 - Treacher Collins syndrome
SOX 10 “ Hirschsprung disease
HOX A-9, 10, 11 - epithelial ovarian cancer
HOX B-5 congenital lung abnormality
Chapter 11: Development of the Limbs
1. An infant exhibits amelia (total absence of a limb). Findings of experimental studies in birds and mice are consistent with the possibility that the limb bud AER failed to express which of the following factors?
A. HOX gene transcription factor
B. Bone morphogenetic substance
C. LIM gene transcription factor
D. WNT gene factor
E. Fibroblast growth factor
2. Recent studies support the likelihood that syndactyly caused by failure of apoptosis between the digital rays may result from disruption of expression of which of the following factors?
A. Bone morphogenetic substance
B. Fibroblast growth factor
C. WNT gene factor
D. Insulin-like growth factor
E. LIM gene transcription factor
3. An infant is born with absence of the ulna and radius and malformations of the carpals and hand. Recent studies show that unique limb segment identities are encoded by HOX genes as follows (scapula - HOX9; humerus - HOX9HOX10; ulna,radius - HOX9HOX10HOX11; proximal carpals - HOX9HOX10HOX11HOX12; distal carpals, metacarpals, phalanges - HOX9HOX10HOX11HOX12HOX13). Therefore, disruption of expression of which of the the following HOX gene families would most likely account for this anomaly?
A. HOX9
B. HOX10
C. HOX11
D. HOX12
E. HOX13
4. An infant born with teratogen-induced phocomelia was probably subjected to which of the following teratogenic substances during the indicated sensitive period.
substance sensitive period
A.
B.
C.
D.
E.
alcohol
thalidomide
phenytoin
cadmium
retinoic acid
4-8 weeks
2-3 weeks
4-8 weeks
2-3 weeks
4-8 weeks
5. In cases of mirror polydactyly, which of the following factors, produced within the early limb bud, is both expressed by and restricted to the newly formed caudal orthotopic ZPA and the cranial ectopic ZPA?
A. BMP4
B. FGF4
C. SHH
D. IGF1