Intro Flashcards
Genes that determine cell identity and positioning during embryonic development
Homeobox (Hox) genes
Number of genes humans have
20,000
Silent substitutions
redundancy of genetic code
Missense mutation
Produce change in single AA
Nonsense mutation
Produce one of the stop codons in mRNA (causes termination)
Frameshift
Result from addition or deletion of number of bases not a multiple of 3
First demonstration that mutation in structural gene could cause AA sub in corresponding protein
Sickle cell (GAG to GTG)
Incidence of newborns with single gene or chromosomal disorder
1:60
Incidence of people under age 25 with genetic disorder
1:20
Types of nontraditional inheritance
Microdeletion, imprinting, trinucleotide repeats
Anticipation
severity increases and younger age of diagnosis as passed from generation to next
Segregation
alleles are paired and each gamete normally receives one member of the pair
Independent assortment
Gene pairs tend to segregate independently of each other
Exception to independent assortment
Linkage
Gene locus
specific location on chromosome
Allele
alternative forms of a gene at given locus
Allelic heterogeneity
different mutant alleles at the same locus produce an abnormal phenotype (ex: CF)
Locus heterogeneity
Mutations at two or more loci cause similar phenotype (ex: retinitis pigmentosa, adult polycystic kidney disease, AD breast cancer)
Adult polycystic kidney disease (APKD)
AD, progressive accumulation of renal cysts (also liver cysts, hypertension, cerebral aneurysms), caused by mutations in genes of PKD1 or PKD2
Pleiotropy
single mutant allele can have widespread effects in different tissues or organ systems (ex: marfan syndrome with cardio, musculoskeletal, and ocular)
Penetrance
proportion of individuals with mutant genotypes that express a mutant phenotype (range 0-1). Complete is 100%
Expressivity
Variability in degree of phenotypic expression seen in different individuals with mutant genotype
True dominant
Heterozygous expression is same as homozygous (ex: HD)
Sex-limited/sex-influenced
expression is affected by sex of individual (ex: male pattern baldness)
Codominant expression example
blood types
AD inheritance
phenotype transmitted generation to generation, each gene carrier has 50% chance of passing each allele to each child, male to male transmission (ex: NF, Marfan, Achondroplasia, OI)
NF1 facts
variable expressivity, AD, 100% penetrance, 50% de novo, neurofibromin maps to 17q
major diagnostic criteria for NF1
six or more cafe-au-lait macules >5 mm prepubertal, >15 postpubertal; two or more neurofibromas of any type and on plexiform neurofibroma; freckling most often axillae or groin; optic glioma; two or more lisch nodules (iris hamartomas); pseudoarthroses; affected 1 degree relative
Penetrance and expressivity are particularly relevant concerning disorders with autosomal dominant inheritance patterns. Your patient has been diagnosed with Osteogenesis imperfecta (OI) caused by variance in the COL1A1 and COL1A2 genes, where not all individuals develop symptoms in their lifetime and even among those with symptoms, some might be more severely affected than others. Your patient mentioned that their mother had the gene but has never had symptoms and that their grandfather carried the gene but had much more severe symptoms than they do.
Which of the following best describes Marfan syndrome
Incomplete penetrance and variable expressivity
Noonan syndrome is a single-gene disorder that presents clinically with short stature,
craniofacial differences, ocular abnormalities, and cardiac malformations, among other
symptoms. Over 15 different genes are associated with Noonan syndrome, including PTPN11, BRAF, and NF1. Within the most commonly associated gene, PTPN11, there are multiple known pathogenic variants affecting different amino acids. Which of the following best describes heterogeneity among this condition
Allelic heterogeneity and locus heterogeneity
