Genetics (Gen Principles) Flashcards
DNA replication
DNA synthesis occurs in the 5’ to 3’ direction ONLY; during DNA replication one daughter strand is synthesized continuously toward the replication fork (leading strand) whereas the other daughter strand is synthesized discontinuously away from the replication fork (lagging strand); the lagging strand is formed from short stretches of newly synthesized DNA separate by RNA primers (Okazaki fragments)
hair loss
androgenic alopecia is the most common cause of hair loss in both males and females; the pattern and severity of the baldness depends on both hormonal (circulating androgens) and genetic factors and vary between males and females; the condition is *POLYGENIC w variable expressivity
TATA box
the TATA box is a promoter region that binds to transcription factors and RNA polymerase II during the initiation of transcription; it is located approximately 25 bases upstream from the beginning of the coding region
Roberstonian translocations
unbalanced Robertsonian translocations account for a minority of Down syndrome cases; karyotyping shows 46 chromosomes w a translocation between 2 Afrocentric non homologous chromosomes (ex: 46, XX, t(14;21))
autosomal recessive inheritance
sickle cell anemia is an AR recessive disorder characterized by a predominance of hbS causing RBCs to sickle, hemolyses and cause vascular obstruction; offspring of the carrier parents have a 3/4 (75%) chance of inheriting at least 1 mutated allele
helicase
during DNA replication and repair, helicase mediates the continuous unwinding of dsDNA at the replication fork
anticipation
an increased number of trinucleotide repeats on the HTT gene is associated w Huntington disease; the larger the number of repeats, the earlier the onset of disease; trinucleotide expansion occurs more frequently during parental transmission, causing a genetic phenomenon called anticipation
linkage equilibrium
two allele loci are said to be in linkage disequilibrium when a pair of alleles are inherited together in the same gamete (haplotype) more often or less often than would be expected given random pairing; this most often occurs when the genes are in close physical proximity on the same chromosomes
locus heterogeneity
mutations at different genetic loci result in similar phenotypes; both parents have oculocutaneous albinism (AR disorder) but they are on *different chromosomes; locus heterogeneity describes when a similar phenotype is produced by mutations in different genetic loci
Xeroderma pigmentosum
Xeroderma pigmentosum a AR disorder characterized by defective nucleotide excision repair often caused by a deficiency in UV-specific endonuclease; affected children usually have severe photosensitivity, hyperpigmentation in sun-exposed areas and a greatly increased risk for skin cancer
inheritance of Down Syndrome
common findings in Down syndrome include cognitive impairment, facial dysmorphism, and cardiac defects; 95% of cases are caused by the presence of an extra chr 21 resulting from nondisjunction; unbalanced robertsonian translocations or mosaicism are less common causes
TATA and CAAT boxes in transcription
the TATA and CAAT boxes are promoters of transcription in eukaryotic cells and are located approx 25 and 75 bases upstream from the transcription start site, respectively; they promote initiation of transcription by serving as binding sites for transcription factors and RNA polymerase II
Poly A tail
the poly-A tail is not transcribed from DNA; instead, it is added as a post-transcriptional modification downstream of the consensus sequence (AAUAA) located near the 3’ end of the mRNA molecule; this tail protects mRNA from degradation within the cytoplasm after it exists the nucleus
transcriptional enhancers and silencers
enhancers and silencers may be located upstream, downstream or within a transcribed gene; these gene sequences function to increase and decrease the rate of transcription, respectively; in contrast, promoter regions are typically 25 or 75 bases upstream (TATA or CAAT) and function to initiate transcription
pleiotropy
pleiotropy describes instances where multiple phenotypic manifestations result from a single genetic mutation; most syndromic genetic illnesses exhibit pleiotropy
heterochromatin
heterochromatin is located at the periphery of the nucleus and composed of heavily methylated DNA and deacetylated histones, causing it to have a low level of transcriptional activity
Xeroderma pigmentosum - defect in nucleotide excision repair
defective nucleotide excision repair often caused by a deficiency in UV-specific endonuclease; affected children usually have severe photosensitivity, hyperpigmentation in sun-exposed areas and a greatly increased risk for skin cancer
Nondisjunction
Nondisjunction is the failure of chr pairs to separate properly during cell division; this could be due to failure of homologous chr to separate in meiosis I or a failure of sister chromatids to separate during meiosis II or mitosis
Homeobox (HOX) genes
HOX genes encode DNA-binding transcription factors that play an important role in the segmental organization of the embryo along the cranio-caudal axis
origin of replication (Ori)
multiple origins of replication make eukaryotic DNA replication quick and effective despite the large size and complexity of the genome compared to that of prokaryotic organisms
MGMT gene
cancer cells alter expression of genes controlling survival and replication by histone modification, transcription factor expression and CpG methylation; methylation of the CpG region adjacent to the MGMT gene, which produces an enzyme that repairs DNA, make tumor cells much more susceptible to alkylating chemotherapy
stop codons
translation of the mRNA template proceeds in the 5’ to 3’ direction; because complementary sequences align in antiparallel fashion, during translation tRNA anticodons will be oriented in the opposite 3’ to 5’ direction; stop codons (UAA, UAG, and UGA) halt protein synthesis by binding a release factor; they do not add amino acids to the polypeptide chain
base excision repair
base excision repair is used to correct single-base DNA defects induced by spontaneously or exogenous chemicals; glycosylases remove the defective base, the corresponding empty sugar-phosphate site is cleaved and removed by the action of endonucelease and lyase; DNA polymerase then replaces the missing nucleotide and ligase seals the final remaining nick
mitochondrial myopathy
mitochondrial dysfunction frequently presents w myopathy, nervous system dysfunction, lactic acidosis and ragged red fibers on muscle biopsy; mitochondrial myopathies due to mtDNA mut are inherited solely in a maternal fashion; only through affects females to all offspring
genetic anticipation in myotonic dystrophy
anticipation describes an inherited condition that presents earlier and w more severe disease in successive generations; in MD, increasing length of the pathogenic trinucleotide repeat expansion accounts for severe hypotonia in a neonate (congenital) and mild symptoms on a parent
nucleolus
the nucleolus is the site of rRNA transcription and ribosomal subunit assembly; RNA polymerase I functions EXCLUSIVELY within the nucleolus to transcribe the 45S pre-rRNA gene, which encodes for most of the rRNA components (18S, 5.8S and 28S rRNAs)
genetic inheritance
nucleotide excision repair
pyrimidine dimers are formed in DNA as a result of UV light exposure; they are recognized by a specific endonuclease complex that initiates the process of repair by *nicking the damaged stand on both sides of the pyrimidine dimer; the damaged segment is then excised, and replacement DNA is synthesized by DNA polymerase
western blotting
used to identify proteins, northern blot is for RNA and southern blot is for DNA
CFTR frameshift mutation
deletion or addition of a number of bases that is not divisible by 3 in the coding region of a gene will cause a frameshift mut; alter reading frame of the genetic code resulting in formation of nonfunctional proteins
alternative splicing
alternative splicing is a process by which a single gene code for various unique proteins by selectively including or excluding different DNA coding regions (exons) into mature mRNA
telomere length
critical shortening in telomere length can signal for programmed cell death; telomerase is a reverse transcriptase (RNA dependent DNA polymerase) that lengthens telomeres by adding TTAGGG repeats to the 3’ end
Duchenne muscular dystrophy mutations
Duchenne muscular dystrophy presents w progressive proximal muscle weakness in young boys due to increased muscle fiber degeneration; it is caused by frameshift mut (most common) or nonsense must leading to the formation of a truncated, defective protein (UAA, UAG, UGA)
Phenylketonuria (PKU) inheritance
intellectual disability, gait abnormalities and a musty odor are signs of PKU a AR disorder; the probability that a child will inherit an AR from heterozygous parents is 1/4
cytoplasmic P bodies
when mRNA is first transcribed from DNA, it is in an unprocessed form called pre-mRNA or heterogenous nuclear mRNA (hnRNA); several processing steps are required before finalized mRNA molecules can leave the nucleus, including 5’-capping, poly A tail addition and intron splicing; cytoplasmic P bodies play an important role in mRNA translation regulation and mRNA degradation
germline BRCA gene mutations
germline BRCA gene mutations dramatically increase the risk for breast and ovarian cancer due to an inability to repair dbDNA breaks; cancers w BRCA mut are often particularly susceptible to tx w platinum compounds (cisplatin) which causes DNA cross-linking requiring repair by BRCA-encoded machinery
