Exam 5 L1+2 Flashcards
Dominant
effects observed in the presence of a normal allele - Heterozygous
Recessive
effects observed in the absence of a normal allele -Homozygous
Autosomal
Chromosomes 1-22
Sex linked
X or Y chromosomes
Autosomal Dominant
DD and Dd, Delayed onset, Huntington disease
Autosomal Recessive
Dd and Dd, early onset, cystic fibrosis uniform
Penetrance
Portion of people with mutated gene that show traits associated with it (population level)
X linked recessive
Xx and Xy small x mutated, onlt males affected, hemophilia A and B, inversion,deletion,missense
Expressivity
Complete to minimal, affected by other genes, harmful chemicals, environment, age
Pathogenic variant
Responsible for causing disease, well supported by research, referred to as mutations
Benign variant
Not responsible for causing disease
strong research to rule out link to disease
Likely benign variant
Probably not responsible for disease, not enough research
Uncertain significance variant
Not confirmed to cause disease, not enough research
Likely pathogenic variant
Probably responsible for disease, not enough research
Inherited variant
passed from parent to child, in every cell of the body
Non inherited variants
occur sometime in person’s life
not in every cell
not passed on
can be caused by environment
Somatic variants
non-inherited, occur in somatic cells (other cells than XY)
New (de novo) variants
Not inherited, may occur in egg or sperm cell no other cells, in egg after sperm and egg unite
Variants during development can lead to mosaicism
Silent mutation
no effect
Missense mutation
Substitution, change amino acid, may produce malfunctioning protein
Nonsense mutation
substitution, change amino acid to stop codon, causes shortening of protein
Insertions and deletions
Switch out 1 or more amino acids
Results in frame shift, multiple of 3 does not shift
Dominant negative
inhibits activity of unmutated protein
Autosomal dominant caused by LOF disease
Familial hypercholesterolemia, mutations in LDL-R, 3000 pathogenic variants reported
Osteogenesis imperfecta LOF dominant effect
Defects in collagen production, 2 subs alpha 1, 1 sub alpha 2
Gain of function
PCSK9 binds to LDLR, instead of recycling, redirects to lysosome
Cystic Fibrosis
Caused by LOF in CFTR, affects fluid secretion and epithelial lining of respiratory, gi, and reproductive tracts, fat malapsorption, bile duct blockage, fat malapsorption.
Triplet repeat mutations
Longer repeats = disruption of gene function, 40 diseases, neurodegeneration associated
Fragile x
Elongated face, protruding ears, low muscle tons, on Y chromosome
FRM1 gene
on x chromosome, most common cause of familial mental retardation, methylation
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 instead of 2, from meiosis 1 nondisjunction, excess skin on back of neck, transverse palm crease, folded ear
Turner syndrome
monosomy x, single x chromosome in females
Mitochondrial mutations
Rare, only inherited from mother (dominant)
Males cant transmit to offspring
Mitochondria have a separate genome that encodes several enzymes involved in oxidative phosphorylation
Affected organs depend most on oxidative phosphorylation (skeletal muscle, heart, brain
Cytogenetic disorders
Frequent 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 are turned off/inactivated when inherited from parents, occurs in ovum or sperm and is transmitted to all somativ cells
Maternal imprinting
silencing of maternal allele
Paternal imprinting
Transcriptional silencing of the paternal allele
prader willi
chromosome 15 deletion from father
angelman syndrome
chromosome 15 deletion from mother
Are missense or inversion/deletions more rare?
missense
