| Flap 1 |
Flap 2 |
| BAX gene |
activates apoptosis - activated by P53 gene if DNA damage is not repairable |
| BCL2 gene |
inhibit apoptosis - prevent mitochondrial leakage of cytochrome c into the cytosol |
| ABL |
nonreceptor tyrosine kinase activity - translocation associated with chronic myelogenous leukemia t(9:22) Philadelphia chromosome |
| HER2/ERBB2 |
synthesizes receptors; amplified in breast carcinoma; is a measure of aggressiveness of breast carcinoma |
| MYC |
Involved in nuclear transcription; associated with the t(8;14) translocation in Burkitt's lymphoma |
| N-MYC |
Involved in nuclear transcription; amplified in neuroblastoma |
| RAS |
Point mutation. Involved in GTP signal transduction; a point mutation leads to leukemia and carcinomas |
| RET |
synthesizes receptors; a point mutation leads to multiple endocrine neoplasia 2a/3b syndromes |
| SIS |
synthesizes growth factors; overexpression of this gene leads to osteogenic sarcoma and astrocytoma |
| Translocation t(9;22) |
Chronic myelogenous leukemia; ABL mutation due to ionizing radiation. Translocation of the ABL gene from chromosome 9 to chromosome 22 and fuses with the break cluster region (BCR) of 22 (Philadelphia chromosome). |
| Translocation t(8;14) |
Burkitt's lymphoma, MYC oncogene, "starry sky" with neoplastic B cells as the dark background and macrophages as the "stars" |
| Translocation t(14;18) |
Follicular B cell Lymphoma. Activates BCL2, the anti-apoptotic gene, which inhibits the release of cytochrome c from mitochondria |
| Translocation t(15;17) |
Acute promyelocytic leukemia |
| Translocation t(12;21) |
favorable prognosis in pre-B-cell acute lymphoblastic leukemia |
| APC |
Adenomatous polyposis coli; associated with familial polyposis (colorectal carcinoma); degrades catenin (which normally activates nuclear transcription) --> prevents nuclear transcription. 5q12 |
| BRCA1/BRCA2 |
regulates DNA repair |
| BRCA2 -- associated with which cancer(s)? |
inactivation is associated with breast CA |
| BRCA1 -- associated with which cancer(s)? |
inactivation is associated with breast, ovarian, and prostate CAs |
| RB |
Inhibits progression from G1 to S phase in the cell cycle. Associated with Retinoblastoma, osteogenic sarcoma, breast carcinoma. RB gene/chromosome13q14: ROB is 13 or 14 - retinoblastoma, ostesarcoma, breast CA |
| TGF-B |
Inhibits progression from G1 to S phase in the cell cycle. Associated with pancreatic and colorectal carcinomas. |
| TP53 |
Point mutation. Inhibits progression from G1 to S phase in the cell cycle; associated with lung, colon, and breast carcinomas. Also repairs DNA and activates BAX gene to initiate apoptosis. |
| VHL |
regulates nuclear transcription; associated with Von Hippel Lindau Syndrome |
| WT1 |
regulates nuclear transcription; associated with Wilms' tumor (11p13), autosomal dominant |
| MEN1 |
associated with increased risk of duodenal ulcers (MEN twice as likely to get it than women!) |
| What is the mutation leading to retinoblastoma? |
point mutation inactivates the RB gene --> no more suppression |
| What is the mutation leading to familial adenomatous polyposis? |
FAP is malignant transformation of polyps --> colorectal cancer before age 50; inactivation of APC suppressor gene |
| Li-Fraumeni syndrome involves what genetic mutation? |
inactivation of TP53 --> increased risk for sarcomas, leukemia, carcinomas before 50 |
| Most variable phase in cell cycle |
G1 |
| G0 Phase of cell cycle |
Resting phase; stable parenchymal cells |
| G1 Phase of cell cycle |
Synthesis of RNA, protein, organelles, and cyclin D; DNA repair; most variable phase |
| S Phase of cell cycle |
Synthesis of DNA, RNA, protein; double the amount of genomic material |
| G2 Phase of cell cycle |
Synthesis of tubulin, necessary for formation of the mitotic spindle |
| Silent mutation |
mutation codes for same aa -- no phenotypic change |
| Missense mutation |
different aa -- phenotypic change |
| Nonsense mutation |
codes for stop codon --> premature termination of protein synthesis |
| Transition mutation |
purine substitution for purine (A for G, or vice versa) or pyrimidine substitution for a pyrimidine (C for T or vice versa) |
| Transversion mutation |
Purine (A or G) replaces a pyrimidine (C or T) |
| Name the purines and pyrimidine and tell which attaches to which in DNA. |
Purines = A and G (purAGe), Pyrimidines = C and T (pyrTC); A-T, C-G |
| Barr body |
In females (usually), the X chromosome that is inactivated and attached to the nuclear membrane |
| What is the difference between nondisjunction and mosaicism? |
Nondisjunction is the unequal separation of chromosomes in meiosis -- 22 or 24 chromosomes end up in the gamete. Mosaicism is the unequal separation of chromosomes in mitosis. |
| Mitrochondial DNA disorders inherited from whom? |
Mother because sperms lose their mitochondria so all a person's mitochondria comes from mom. |
| What happens in embryonic sexual differentiation when there is no Y chromosome? |
Wolffian ducts --> apoptosis. The default pathway is to have keep the female structures. |
| What happens in embryonic sexual differentiation when there is a Y chromosome? |
Sertoli cells make MIF (Mullerian inhibitory factor) --> Mullerian ducts --> apoptosis --> keep male structures. |
| what is genetic anticipation? |
phenomenon whereby a disease presents at an earlier age (with deeper penetrance) as it's passed down through generations; happens with trinucleotide repeat diseases |
| name three trinucleotide repeat diseases |
Huntington's, Duchenne muscular dystrophy, fragile X. TriNUC (3 bombs): 3D (Duchenne) Hunting -- aim for the X. |
| What is a chromosomal pericentric inversion? |
An inversion in which the breakpoints occur on both arms of a chromosome. The inverted segment includes the centromere. perI --> Includes centromere. |
| What is a chromosomal paracentric inversion? |
An inversion in which the breakpoints occur on both arms of a chromosome. The inverted segment does NOT include the centromere. perI --> INcludes centromere. parA doesn't have an I so it doesn't INclude. |
| What is a restriction fragment length polymorphism? |
RFLP. a variation in the DNA sequence of a genome which can be detected by a laboratory technique known as gel electrophoresis; important in genome mapping & locating genetic disease genes. The basic technique for detecting RFLPs involves the fragmentat |
| Resistance transfer factor |
bacterial plasmid that encodes one or more drug resistance genes & has capability of mediating its own transfer to another bacterium during conjugation. Most have formed by the accumulation of transposons into fertility factor plasmids. |
| How do transposons insert themselves into a new location? |
site-specific recombination. Flanking DNA sequences of a transposon are indirect repeats that are complimentary and antiparallel to one another. SSR is when transposons create direct repeats to insert their mobile DNA. |
| tra operon |
Transfer operon. Genes necessary for non-sexual transfer of genetic material in bacteria. The tra genes encode proteins which are useful for the propagation of the plasmid from the host cell to a compatible donor cell or maintenance of the plasmid. |
| mutations involved in adenoma carcinoma of colon |
APC, RAS, TP53 |
| Mutations in DNA mismatch genes |
Colon cancer |
| germline mutation of NF2 gene at long arm of chromosome 22 (22q) |
bilateral acoustic neuroma (tumor on CN8 - acoustic nerve) |
| germline mutation of NF1 gene at long arm of chromosome 17 (17q11) |
neurofibromatosis type 1 |
| Name two genetic mechanisms that can lead to either Angelman syndrome or Prader Willi. |
Genomic imprinting or uniparental disomy. |
