Diseases

Question 1

Sickle Cell Anemia

Answer 1

E6V mutation (one aa mutation; beta globin gene)
destroys MstII restriction site

Question 2

Cystic Fibrosis

Answer 2

CFTR mutation; deletion of F508 –> protein misfolding

Question 3

amyloidosis

Answer 3

systemically dispersed misfolded proteins

Question 4

HD, SCA1, MJD/SCA3, kennedy disease, SBMA, DRPLA, myotonic dystrophy

Answer 4

triplet CAG repeats

Question 5

gout

Answer 5

accumulation in tissues of purins
–> uric acid buildup

defect in phosphoribosyl synthetase

Question 6

Lesch-Nyhan Disease

Answer 6

purin accumulation

defect in hypoxanthine-guanine phosphoribosyl transferase

Question 7

Colon cancer

Answer 7

APC mutations

Question 8

Hemoglobin Wayne

Answer 8

chronic anemia

3’ terminal frameshift mutation (delete U)

Question 9

Hemoglobin Constant Spring

Answer 9

UAA stop codon to CAA Gln

chronic anemia

Question 10

X-linked dyskeratosis congenital

Answer 10

IRES-dependent translation impaired = insufficient levels of anti-apoptotic and cell-cycle control proteins

Question 11

Phenylketonuria

Answer 11

excess Phe in urine

Question 12

Cystinuria

Answer 12

excess cysteine in urine; issue with cysteine transporter

Question 13

Congenital disorder of glycosylation (CDG)

Answer 13

malfunctions in glycosylation pathways

Question 14

Li Fraumeni syndrome

Answer 14

mutated p53 or Chk2 gene

high risk for cancer

Question 15

ataxia telangiesctasia mutated syndrome (ATM)

Seckel syndrome

Answer 15

mutations in proteins crucial for DNA checkpoint function

high risk of cancer, neurological defects

Question 16

breast cancer, ovarian cancer

Answer 16

Mutations in BRCA-1/BRCA-2 → DNA damage not recognized and repaired → chromosomal breakage and abnormal recombination events; “genomic instability” phenotype

Question 17

retinoblastoma

Answer 17

mutations in RB tumor suppressor protein

Question 18

glioblastomas

Answer 18

MGMT silenced via promoter methylation

Question 19

xeroderm pigmentosa (XP)

Answer 19

defects in global NER

Question 20

cockayne syndrome (CS)

Answer 20

defects in transcription-coupled NER

Question 21

HNPCC (lynch syndrome)

Answer 21

mutations in MMR genes (MSH2, MLH1)

Question 22

tumor metastasis

Answer 22

abnormal splicing of CD44

splice variants diagnostic and prognostic tools

Question 23

Marfan syndrome

Answer 23

mutations that affect splicing of fibrillin gene

Question 24

β-Thalassemia

Answer 24

Inherited anemia; mutation in β-globin promoter → reduce amount of β-globin protein produced (clinically mild)

Question 25

γδβ-Thalassemia

Answer 25

Deletion of the locus control region (LCR) of β-globin gene cluster; LCR = essential for transcription of all genes in cluster
bad anemia

Question 26

Hemophilia B Leyden

Answer 26

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)

Question 27

Fragile X Syndrome

Answer 27

CGG repeat in 5’ region of FMR1 gene → methylation cytosine residues in CpG islands → transcriptional inactivation of FMR1 gene

Question 28

Craniosynostosis

Answer 28

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

Question 29

Androgen Insensitivity Syndrome (AIS)

Answer 29

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

Question 30

Wardenberg Syndrome type II

Answer 30

Deafness, pigmentation defects (eyes, hair, skin)
Mutations in MITF gene (bHLH DNA binding protein)
Gene encodes TF involved in melanocyte development

Question 31

malignant rhabdoid tumors

Answer 31

Childhood cancer

Associated with truncating mutations in hSNF5/INI1 gene (encodes chromatin-remodeling SWI/SNF complexes)

Question 32

Rubinstein-Taybi Syndrome

Answer 32

Mutation in CREB binding protein (CBP) → CBP (=HAT) haploinsufficiency → affects transcription of multiple target genes

Question 33

Leukemia

Answer 33

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

Question 34

Alpha-thallasemia

Answer 34

Polyadenylation signal mutation