Diseases note cards HB1.txt

HBA1 and HBA2 deletion, alpha-globin chromosome 16, unequal crossing over and homologous pairing, autosomal recessive, reduction in the production of alpha-globin

deletion of B-globin genes, frameshift or nonsense mutation, major: homozygote, impaired RNA synthesis, impaired primary mRNA,

downregulation two beta-globin genes minor: heterozygote

imprinting-defect in the maternal gene inactivation of deletion on chromosome 15 mental retardation, ataxia

imprinting-defect in the paternal gene inactivation of paternal allele that is normally active mental retardation, obesity, hypotonia, hyperphasia

LDL-Receptor gene, chromosome 19 Alu repeats-->unequal crossing over inability to bind cholesterol, high cholesterol

Dystrophin gene Mutation in very long gene X-linked recessive progressive neuromuscular disorder

NER coupled gene NER mutation-->inability to repair thymine dimers autosomal recessive inability of Nucleotide Excision Repair (NER)--> unable to repair DNA damage from UV because thymine-dimers require NER, skin malginancy first, then neuro

NER coupled gene, not the XP gene NER mutation autosomal recessive

MSH2 and MLH1 (60%) MSH1 and PMS2 also involved Error in msmatch repair-->Microsatellite instability autosomal dominant Mutations in MMR lead to inability to repair single nucleotide errors-->tumors in proximal colon (sometime endometrium, urinary tract, stomach), 90% are MSI-H or MSI-L

chromosome 17 stem loop is destabilized as a result-->causes increase recognition of exon 10 Related to Alzheimers

translocation from chromosone 9-->22 (philadelphia chromosome, ABL BCR genes) Puts regulatory region in the wrong place N/A myeloid stem cell proliferation, splenomegaly

CFTR (chromosome 7) Poly T tract-homozygous loss of cAMP ion channel malfunction- cells cannot maintain osmolality, missfolded proteins in PDZ domain autosomal recessive severe pulmonary disease, male infertility

MECP2 (X-chrome) Inability to recruit binding proteins to methylated sites at CpG islands X-linked dominant DNF build up in the brain leading to severe neurological disorders and mental retardation

Dominant negative protein aggregates in brain unknown,role of glutamate and myelnation familial account for 5-10% death of upper and lower motor neurons-->muscle twitching, weakness, muscle atrophy

defect in ankyrin binding Autosomal dominant hemolytic anemia, splenomegaly, RBCs are tennis ball-like

defect in spectrin self association site to form the slinky Autosomal dominant hemolytic anemia, splenomegaly, RBCs are elliptical

post-translational modification in enzymatic processing Deficiency in glucocerebrosidase fatty accumulations spleen, liver, kidney, brain, blood, bone marrow THERAPY: GENZYME

B-globin gene, point mutation from Glutamate to Valine Hb-S polymerizes in deoxygenated conditions Autosomal co-dominant Anemia, joint pain, jaundice, splenomegaly

triglyceride (LDL) accumulation in arteries high cholesterol (LDL accumulation)

lactase enzyme activity decreased with age deficiency in the lactase enzyme abdominal cramping, indigestion

deficiency in N-acetylglucose 1 P transferase substrate for that enzyme builds up in the lysosome and inclusion bodies seen in fibroblasts extracellular matrix substrate for that enzyme builds up in the lysosome and inclusion bodies seen in fibroblasts extracellular matrix

phospholipid synthesis enhanced because of IgEs (anaphylactic shock)

collagen type III defect involved the mutation in collagen processing hyper flexible joint, joint disease

abnormal type I collagen autosomal dominant multiple factors with minimal trauma, hearing loss, dental imperfcetion

• affects dynein autosomal dominant "situs inversus, patients have underlying ciliopathy, Chrnoic sinusitis, chronic bronchitis because of the inability of the cilia to move mucous through the lungs
• "

DHCR7 deficiency--> cholesterol deficiency (SLO No Cho-lesterol) rare cholestrol deficiency leads to multiple congenital abnormalities

not genetic but affects the CFTR toxin binds to GM1 ganglioside, A subunit dissociates, B enters cell--cAMP permanently on, loss of Cl- from cell, low Na+ inside diarrhea, rice water stool, dehyrdation

Fibroblast Growth Factor Receptor 3 (FGFR3) Autosomal dominant short limbed dwarfism, short limbed intelligence

ABO blood group gene-Chromosome 9 convert precursor H antigen to A or B antigen, O allele0enzyme with no function Autosomal co-dominant ABO gene 7 exons, exon 7 is largest, exon 6 has allele for deletion in "O" ABO antigens expressed on RBCs, epithelial and endothelial cells

X-linked recessive factor XIII bleed easily X-linked recessive

endopeptidase gene inability of kidney tubules to reabsorb phosphate X-linked dominant short stature

Triallelic inheritance obesity, rentinits pigmentosa, polydactyly, mental retardation, renal failure

Mitochondrial inheritance, Degeneration of retinal ganglion cells and their axons-acute loss of central vision

Point mutation at position disrupts the mitochondrial gene for tRNA-Lys disrupts synthesis of oxidative phos proteins

Variable expressivity Within the same family you can have different levels of expressivity (deafness, pigment changes, etc)

RET gene gain of function mutation of RET example of phenotypic variation multiple endorine neoplasia

RET gene loss of function mutation of RET example of phenotypic variation defective colonic motility--constipation

trisomy 21, spontaneous, AMA implicated Facial dysmorphia, cardiac disease and Leukemia (top 2), Hypothyroid, Hearing screens

trisomy 13, spontaneous, rare 1: 25000 facial dysmorphia

trisomy 18, spontaneous, rare 1: 25000 distinct head shape, facial dysmorphia, rocker bottom feet

deletion on chromosome 17, 175-250 bp repeats cause deletion autosomal spontaneous

duplication on chromosome 17, 175-250 bp repeats cause deletion autosomal spontaneous, same gene as Smith Magenis, but duplication causes different phenotype

deletion of chromosome 15, 400 bp repeats cause deletion autosomal spontaneous exhibits the concept of imprinting and uniparental disomy, when the allele is mutated on the maternal or paternal allele

deletion on chromosome 22, 225-400 bp repeats autosomal spontaneous velocardiofacial syndrome,

47 XXY or 48XXXY Tall thin, long legs, hypogonadism, infertility, mild learning disabilities, psychosocial adjustment

extra Y 47 XYY Normal phenotype and fertility, but lower IQ, can be more aggressive

extra X female 47, XXX Tall stature, usually fertile, lower IQ, detected by testing for fragile X syndrome

loss of X, 45 X, Less common than the other, Broad flat chest, webbing of neck, short stature, Average to above average intelligence, nonverbal IQ<<verbal IQ

• NF1 gene--loss of function mutation--autosomal dominant
• Variable expressivity in the production of neurofibrin
• Cafe au lait spots, benign fleshy tumors, Lish nodules in the iris of the eye

• Unstable CAG repeats s-polyglutamine disorder (less amount of repeats necessary to cause disease)--autosomal dominant--gain of function mutation
• Normal has 9-35 repeats, HD has 40 or more repeats
• Causes conitive abnormalities, neurodegenerative disase

CAG repeats

• FMR1 gene on X--many CGG repeats in the 5' UTR region of the first exon of FMR1
• Normal has 60-200, Fragile X has greater than 200
• Chromatin fails to condense during mitosis
• Penetrance is 50-60% in females, affects males more
• Most common form of HERITABLE mental retardation
• Carriers of pre-mutation can have FX associated tremor and ataxia

• CTG repeats, normal is 5-30, diseas is 50-80, autosomal dominant
• Noterious for lack of penetrance and variable expressivity
• Clear evidence of anticipation
• Muscular dystrophy, cataracts, hypogonadism

Copper ATPas pump, affect neurological function

hypercoagulation caused by the defect in Factor V--> overactivity of clotting Protein C

inversion aberrant, evident in 45% of all non-familial Hemophilia A

example of imprinting, macroglossia

glycolipid associated disease, autoimmune attack of Schwann cells