Diseases Flashcards
Sickle Cell Anemia
E6V mutation (one aa mutation; beta globin gene) destroys MstII restriction site
Cystic Fibrosis
CFTR mutation; deletion of F508 –> protein misfolding
amyloidosis
systemically dispersed misfolded proteins
HD, SCA1, MJD/SCA3, kennedy disease, SBMA, DRPLA, myotonic dystrophy
triplet CAG repeats
gout
accumulation in tissues of purins
–> uric acid buildup
defect in phosphoribosyl synthetase
Lesch-Nyhan Disease
purin accumulation
defect in hypoxanthine-guanine phosphoribosyl transferase
Colon cancer
APC mutations
Hemoglobin Wayne
chronic anemia
3’ terminal frameshift mutation (delete U)
Hemoglobin Constant Spring
UAA stop codon to CAA Gln
chronic anemia
X-linked dyskeratosis congenital
IRES-dependent translation impaired = insufficient levels of anti-apoptotic and cell-cycle control proteins
Phenylketonuria
excess Phe in urine
Cystinuria
excess cysteine in urine; issue with cysteine transporter
Congenital disorder of glycosylation (CDG)
malfunctions in glycosylation pathways
Li Fraumeni syndrome
mutated p53 or Chk2 gene
high risk for cancer
ataxia telangiesctasia mutated syndrome (ATM)
Seckel syndrome
mutations in proteins crucial for DNA checkpoint function
high risk of cancer, neurological defects
breast cancer, ovarian cancer
Mutations in BRCA-1/BRCA-2 → DNA damage not recognized and repaired → chromosomal breakage and abnormal recombination events; “genomic instability” phenotype
retinoblastoma
mutations in RB tumor suppressor protein
glioblastomas
MGMT silenced via promoter methylation
xeroderm pigmentosa (XP)
defects in global NER
cockayne syndrome (CS)
defects in transcription-coupled NER
HNPCC (lynch syndrome)
mutations in MMR genes (MSH2, MLH1)
tumor metastasis
abnormal splicing of CD44
splice variants diagnostic and prognostic tools
Marfan syndrome
mutations that affect splicing of fibrillin gene
β-Thalassemia
Inherited anemia; mutation in β-globin promoter → reduce amount of β-globin protein produced (clinically mild)
γδβ-Thalassemia
Deletion of the locus control region (LCR) of β-globin gene cluster; LCR = essential for transcription of all genes in cluster
bad anemia
Hemophilia B Leyden
X-linked disorder, affects clotting. Mutations in DNA control element in promoter of Factor IX gene (prevents binding appropriate transcriptional activators). Overcome (→ 60%) at puberty when androgen receptor becomes active (some overlap b/w two)
Fragile X Syndrome
CGG repeat in 5’ region of FMR1 gene → methylation cytosine residues in CpG islands → transcriptional inactivation of FMR1 gene
Craniosynostosis
Mutation in homeodomain protein MSX2 → one aa mutation that makes DNA bind more strongly → GOF mutation → affects transcription of other genes that cause suture closure
Androgen Insensitivity Syndrome (AIS)
Femininzation of external genitalia, abnormal secondary sexual devl in pubery, infertility.
Mutations in either DNA binding domain or ligand binding domain of androgen receptor (zinc finger DNA binding protein) → less responsive to androgens
Wardenberg Syndrome type II
Deafness, pigmentation defects (eyes, hair, skin)
Mutations in MITF gene (bHLH DNA binding protein)
Gene encodes TF involved in melanocyte development
malignant rhabdoid tumors
Childhood cancer
Associated with truncating mutations in hSNF5/INI1 gene (encodes chromatin-remodeling SWI/SNF complexes)
Rubinstein-Taybi Syndrome
Mutation in CREB binding protein (CBP) → CBP (=HAT) haploinsufficiency → affects transcription of multiple target genes
Leukemia
Hematopoietic malignancy. Chromosomal translocations leading to GOF fusion proteins, some of which involve fusions of transcriptional regulators with HATs or HDACs = alter activity of regulators
Alpha-thallasemia
Polyadenylation signal mutation
