Chromosomes/Genes/ GeneticMarkers Flashcards
Marfan - MoI, gene, Chromosome
FBN1 gene mutation on chromosome 15; AD
ex of missense mutation
Sickle Cell (glutamic acid w/ valine)
Becker?
Ex of frameshift mutation
Duchenne muscular dystrophy, Tay-Sachs disease.
Splice cite mutation
rare causes of cancers, dementia, epilepsy, some types of β-thalassemia.
Issue with Nucleotide excision repair
Defective in xeroderma pigmentosum (inability to repair DNA pyrimidine dimers caused by UV exposure).
Mismatch repair
Lynch syndrome; serrated polyps
issue with Nonhomologous end joining
ataxia-telangiectasia.
Homologous recombination issue
defective in breast/ovarian cancers with BRCA1 mutation and in Fanconi anemia.
mutated PEX genes - Dz, MoI
Zellweger syndrome—autosomal recessive disorder of peroxisome biogenesis. Hypotonia, seizures, hepatomegaly, early death.
mutation in ABCD1 gene - dz, MoI
Adrenoleukodystrophy—X-linked recessive disorder of β-oxidation due to mutation in ABCD1 gene –> VLCFA buildup in adrenal glands, white (leuko) matter of brain, testes. Progressive disease that can lead to adrenal gland crisis, coma, and death.
COL1A1 and COL1A2
Osteogenesis Imperfecta
COL5A1, COL5A2
Classical EDS
type III procollagen (eg, COL3A1
EDS vascular type
ATP7A - Dz, MoI
Menke’s XLR
ATP7B, Dz, MoI, Chr
Wilson’s - AR, Chr 13
ex of Pleiotropy
One gene contributes to multiple phenotypic effects. Untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor.
Homocyteinuria, any syndrome
due to Gs-protein activating mutation.
McCune-Albright syndrome—due to Gs-protein activating mutation.
Presents with unilateral café-au-lait spots A with ragged edges, polyostotic fibrous dysplasia (bone is replaced by collagen and fibroblasts), and at least one endocrinopathy (eg, precocious puberty).
Lethal if mutation occurs before fertilization (affecting all cells), but survivable in patients with mosaicism.
Ex of locus heterogeneity
Mutations at different loci can produce a similar phenotype.
Albinism.
Allelic heterogeneity
Different mutations in the same locus produce the same phenotype.
β-thalassemia.
Associated with a mutation or deletion of chromosome 15 of paternal origin.
Prader Willi
Associated with mutation or deletion of the UBE3A gene on chromosome 15.
Angelman
XLD diseases
Hypophosphatemic rickets, fragile X syndrome, Alport syndrome, focal dermal hypoplasia, Rett syndrome
CFTR - deletion? chromosome?
deletion of Phe 508, chr 7
DMD gene - dz?
dystrophin gene, Duchenne & Becker
DMPK gene - what mutation,dz
Autosomal dominant. CTG trinucleotide repeat expansion in the DMPK gene –> abnormal expression of myotonin protein kinase
Myotonic type 1 dystrophy
MECP2 - which chr, dz?
Rett syndrome, X chr
sx/ cognitive difficulties, ataxia, seizures, growth failure, hand wringing
Methyl CpG binding protein 2 = MECP2, needed for nerve cell function
FMR1 gene - mut’n? dz? MoI?
Fragile X syndrome
X-linked dominant inheritance. Trinucleotide repeat in FMR1 gene –> hypermethylation –> dec expression.
Chr 3
von Hippel-Lindau disease, renal cell carcinoma
chr 4
ADPKD (PKD2), achondroplasia, Huntington disease
chr 5
Cri-du-chat syndrome, familial adenomatous polyposis
chr 6
Hemochromatosis (HFE)
chr 7
Williams syndrome, cystic fibrosis
chr 9
Friedreich ataxia, tuberous sclerosis (TSC1)
chr 11
W11ms tumor, β-globin gene defects (eg, sickle cell disease, β-thalassemia), MEN1 (MEN11)
Mantle cell (11:14) Marginal cell (11:18)
chr 13
Patau syndrome, Wilson disease, retinoblastoma (RB1), BRCA2
chr 15
Prader-Willi syndrome, Angelman syndrome, Marfan syndrome
Tay Sachs (Hexoaminidase A)
chr 16
ADPKD (PKD1), α-globin gene defects (eg, α-thalassemia), tuberous sclerosis (TSC2
chr 17
Neurofibromatosis type 1, BRCA1, TP53
chr 18
Edwards syndrome
chr 21
Down syndrome
chr 22
Neurofibromatosis type 2, DiGeorge syndrome (22q11)
Congenital microdeletion of long arm of chromosome 7
Williams syndrome
distinctive “elfin” facies, intellectual disability, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems (eg, supravalvular aortic stenosis, renal artery stenosis). Think Will Ferrell in Elf.
genetic deficiency of FOXP3
IPEX - IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome— genetic deficiency of FOXP3
Characterized by enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infant
PIGA gene
Paroxysmal nocturnal hemoglobinuria
preventing the formation of glycosylphosphatidylinositol (GPI) anchors for complement inhibitors, such as decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59)
Defect in BTK
X-linked (Bruton) agammaglobulinemia
22q11 microdeletion
DeGeorge syndrome
STAT3 mutation
Autosomal dominant hyper-IgE syndrome (Job syndrome)
Deficiency of Th17 cells due to STAT3 mutation
defects in AIRE.
Chronic mucocutaneous candidiasis
failure to detect DNA damage
Ataxia-telangiectasia
Defects in ATM gene
Mutation in WAS gene;
Wiskott Aldrich - leukocytes and platelets unable to reorganize actin cytoskeleton –> defective antigen presentation;
lysosomal trafficking regulator gene (LYST)
Chédiak-Higashi syndrome
PLAIN:
Progressive neurodegeneration,
Lymphohistiocytosis,
Albinism (partial),
recurrent pyogenic Infections,
peripheral Neuropathy.
Giant granules in granulocytes and platelets. Pancytopenia. Mild coagulation defects.
Genes for the following 5 bacterial toxins are
encoded in a lysogenic phage
(ABCD’S):
Group A strep erythrogenic toxin, Botulinum toxin,
Cholera toxin, Diphtheria toxin, Shiga toxin.
These bacterial toxins inactivate 60S ribosome by removing adenine from
rRNA
Shigella,
EHEC (shiga like toxin)
MRSA (methicillin-resistant S aureus)—
important cause of serious nosocomial and
community-acquired infections; resistance
due to altered penicillin-binding protein.
______ gene from staphylococcal chromosomal
cassette involved in penicillin resistance.
MecA
All DNA viruses have dsDNA genomes except
_______ (ssDNA).
Parvo
All RNA viruses have ssRNA genomes except
_________ (dsRNA).
Reoviruses
Reo - like Duo (2)
Bacterial catalase peroxidase
(encoded by ____) needed to
convert INH to active metabolite.
KatG
Gene affected in familial dilated cardiomyopathy
what type of mutation?
TTN, affects titin protein, connects myosin heavy chain with Z disc
nonsense mutation
QID13600
Gene affected in familial bicuspid aortic valve
NOTCH1
Due to transthyretin gene mutation
Familial amyloid polyneuropathies
