Exam 5 Exam Material Flashcards
Autosomal dominant
DD and Dd, Delayed onset, Huntington disease
Autosomal recessive
Dd and Dd, Early onset, uniform symptoms
X linked recessive
Xx and Xy, Only males effected usually, Hemophilia A an B
Penetrance
Portion of people in population with mutated gene that shows traits
Expressivity
How a gene presents itself, complete, moderate, minimal, no penetrance/expression
Genetic variants
Pathogenic, Benign, Likely Pathogenic, Likely benign, Uncertain significance
New de novo variants
Found in children not parents, in egg or sperm of parents but not in other cells, can lead to mosaicism
Missense mutation
Change 1 nucleotide, amino acid to different amino acid, produce malfunctioning proteins
Nonsense mutation
Single nucleotide change, change amino acid to stop codon, causes frame shift, multiple of 3 does not cause frame shift
Three types of mutations that cause autosomal dominant disorders
Loss of function, Osteogenesis imperfecta, gain of function
Loss of function
Loss of LDL-R
can’t remove LDL from body
Familial hypercholesterolemia
Osteogenesis imperfecta
Defects in production of collagen
2 subunits alpha 1, 1 subunit alpha 2
Gain of function
PCSK9 binds to LDL receptor
Directs it to lysosome
Cystic fibrosis
Recessive disorder LOF, most common affecting Caucasians, affects fluid secretion in exocrine glands, respiratory lining, GI, and reproductive tracts
Translocation
transfer part of a chromosome to another
Isochromosome
Centromere divides horizontally instead of vertically
Deletion
Loss of a portion
Inversion
Two interstitial breaks the segment reunites but is flipped
Ring chromosome
A variant of deletion after loss of segments from each end of the chromosome, the arms unite to form a ring
Down syndrome
Trisomy 21, 3 copies, meiosis 1 nondysjunction, excess skin on back of neck, transverse palmar crease, folded ear
Turner syndrome
Monosomy X, single X chromosome in females
Triplet repeat mutations
Longer repeats cause disruption of gene function
40 neurodegeneration diseases, fragile X
Mitochondrial mutations
Only inherited from mother, males can’t transmit to offspring, affected organs depend on oxidative phosphorylation (skeletal muscle, heart, brain)
Cytogenetic disorders
In 1/200 infants, change in chromosome number or structure, autosomes or sex chromosomes, disorders from autosome number are more severe than single gene disorders
Genetic imprinting
Some regions of DNA inactivated in copy received from mother or father
Maternal imprinting
silencing of maternal allele
Paternal imprinting
Transcriptional silencing of paternal allele
Prader willi
Chromosome 15 deletion from father
Angelman syndrome
chromosome 15 deletion from mother
Neoplasia
Abnormal growth of cells and tissues
characterized by dysregulated cell proliferation
Difference between malignant and benign
Cancers are less differentiated, invasive, and metastatic
Grading
estimate of aggressiveness level of malignancy
based on differentiation and greater clinical value
Three fundamental principles of carcinogenesis
Genetic changes lie at the heart of carcinogenesis, carcinogenesis is multistep, oncogenes and tumor suppressive genes are targets of this damage
Oncogenes
genes that encode proteins that inhibit cancer
Two hit hypothesis
Need a mutation in both genes to lose activity of tumor suppressor and to develop cancer
Pediatric cancers
Tend to have single genetic events that are important at a specific developmental time
Adult cancers
rarely have a single genetic mutation
X ray and cosmic radiationcause
genetic lesions
Six hallmarks of cancer cells
Self sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasis
Limitless replicative potential
Sustained angiogenesis
Evading apoptosis
G0/G1
Building blocks, duplicated contents but not chromosomes
G1 checkpoint
Cell size, nutrients, dna damage, growth factors
S
cell replicating DNA
G2
cell assembles for chromosome segregation and cytokinesis
double checks duplicated chromosomes
M
mitosis, spindle assembly checkpoint
Telomerase expression
Leads to cell immortalization, limitless replicative potential, telomeres at the end of chromosomes shorted with every division
How tumor cells induce angiogenesis
Produce vascular endothelial growth factor
How inflammation increases cancer risk
Results in persistent regenerative cell proliferation or hyperplasia and dna damage as a result of reactive oxygen and nitrogen species produced by immune cells
PTEN
Phosphatase that reverses PI3K kinase phosphorylation
NF1
Inhibits Ras
BAX
pro-apoptotic regulators
VEGF
promotes angiogenesis
LMP1 and LMP2
In Epstein Barr virus, cell surface receptors that activate mitogenic signaling in B cells
vFLIP
In Kaposi’s herpesvirus, increases metastasis and angiogenesis
MCPV
Merkel cell polyomavirus, requires infection then mutation of the large T antigen in elderly and immunocompromised
HPV
Human papillomaviruses cause cervical cancer because E6 targets p53 and E7 targets Rb
TAX
In HTLV-1, increases expression of genes that promote proliferation, DNA repair, and resistance to apoptosis
Loss of APC
results in hyperproliferative colonic epithelium
GOF mutation of ras gene
Intermediate adenoma
Loss of mutation of p53
results in carcinoma
HER2 overexpression
Breast cancer responsiveness to anti-hormone therapy
