CASE 1
pleiotropy: single gene affects two or more, seemingly unrelated, phenotypes
compound disease: caused by combinatorial effect of multiple mutant alleles
- heterozygous: trans > compound disease; cis > carrier of two traits
nonsense mutation: codon changed to stop codon > nonfunctional protein
translocation: exchange of segments between two different chromosomes
haploinsufficiency: single gene copy isn’t enough to express trait
pseudogene: defective result of gene duplication, structurally resembles gene but doesn’t
code for protein
SCD is a qualitative problem, thalassemia is a quantitative problem
order: transcription, capping, cleavage, polyadenylation, RNA splicing
addition extra exon, in intron, creates new splice site and makes cryptic splice site active,
cryptic splice site is normally not used
iron lies outside plane in deoxy-hemoglobin, binding oxygen causes rearrangement of
electrons in Fe-ion > ion becomes smaller; electron is partially delocalized to oxygen >
superoxide ion; > iron moves into plane
hydrogen bonding to second histidine, prevents release superoxide ion
CASE 2
CASE 3
nucleosomes are obstacle for transcription
methylation in non-divinding cells: make DNA more accessible for transcription-related
proteins
methylation in mitosis: opening chromatin structure for replication
chromatin: package genome in nucleus and gene expression regulation
histone genes don’t have introns
methylation histones > condensed/compact heterochromatin
nuclease digests linker DNA
acetylation: more open chromatin, less tight interaction DNA-nucleosome
DNA transposon: cut-paste
retrotransposon: copy-paste (RNA intermediate > DNA intermediate)
- integrase
DNA and histone methylation silences transposon transcription
epigenetic modifications: reversible, not transferred to offspring
epigenetics: changes in gene expression that don’t involve changes to underlying DNA seq
- change in phenotype without change in genotype
DNA methylation is often maintained over generations
detection DNA methylation: bisulphite sequencing (chemical conversion C>U) or methylation
sensitive restriction enzymes
detection histone modification: ChIP seq
detection small RNAs: deep sequencing
detection active transposons: transposon display
CASE 4
auxin recognized by (TIR1) receptor protein complex
receptor (E2) transfers Ub to substrate (= Aux/IAA)
poly-ubiquitylated Aux/IAA proteins is degraded by proteasome
ARF (auxin response factor) promotes transcription
- binds DNA as dimer at high affinity
,TPL (topless) inhibit transcription
mono-ubiquitylation: changing location or activity of proteins
acetylation: neutralizes charge DNA and histones > weakened bond
two-hybrid system: study protein-protein binding interactions (bait-prey)
disassortative: high degree nodes tend to attach to low degree nodes
robustness allows system to maintain functions against disruptions
coherent feed forward loop: indirect path has same sign as direct path
complementation: expression of multiple genes in pathway is necessary to obtain specific
function
gene interaction: genes at multiple loci determine single phenotype
epistasis: effect of one gene depends on effect of other gene
ChIP: determine TF binding sites in genome
CASE 5
Ames test to check mutagenic strength of carcinogens
- use plate without histidine to check for mutated DNA
ionizing radiation > doublestrand DNA breaks > deletions, duplications, inversions etc
aneuploidy: abnormal number chromosomes in cell
oncogene is mutated version of proto-oncogene
angiogenesis: new blood vessels formed
phosphorylation: serine, threonine, tyrosine
ubiquitilation: lysine (isopeptide bonds)
Fundamental genetics concepts
genetic terms:
gene = inherited factor which determines a characteristic
allele = one of more alternative forms of a gene; variant of sequence of nucleotides at
particular location/locus on DNA molecule
locus = specific place on the chromosome
genotype = set of alleles possessed by individual
phenotype / trait = appearance or manifestation of a characteristic
heterozygote = individual possessing two different alleles at the locus
homozygote = individual possessing two equal alleles at the locus
,one gene: one ORF; alternative splicing (→ different mRNAs)
post-transcriptional modification: RNA primary transcript is chemically altered following
transcription from gene to produce mature and functional RNA molecule that can then leave
the nucleus and perform any of a variety of different functions in the cell
genes confer phenotypes
regulatory elements: binding sites for transcription factors; involved in gene regulation
DNA > pre-mRNA > mRNA > polypeptide
startcodon: methionine
, genetic variation due to recombination
law of segregation: during gamete formation, the alleles for each gene segregate from each
other so that each gamete carries only one allele for each gene and offspring acquire one
allele from each parent
law of independent assortment: genes for different traits can segregate independently during
the formation of gametes and the laws of chance govern which particular characteristics of
the parental pairs will occur in each individual offspring, the principle of independent
assortment results from the independent separation of chromosomes during meiosis
pleiotropy: single gene affects two or more, seemingly unrelated, phenotypes
compound disease: caused by combinatorial effect of multiple mutant alleles
- heterozygous: trans > compound disease; cis > carrier of two traits
nonsense mutation: codon changed to stop codon > nonfunctional protein
translocation: exchange of segments between two different chromosomes
haploinsufficiency: single gene copy isn’t enough to express trait
pseudogene: defective result of gene duplication, structurally resembles gene but doesn’t
code for protein
SCD is a qualitative problem, thalassemia is a quantitative problem
order: transcription, capping, cleavage, polyadenylation, RNA splicing
addition extra exon, in intron, creates new splice site and makes cryptic splice site active,
cryptic splice site is normally not used
iron lies outside plane in deoxy-hemoglobin, binding oxygen causes rearrangement of
electrons in Fe-ion > ion becomes smaller; electron is partially delocalized to oxygen >
superoxide ion; > iron moves into plane
hydrogen bonding to second histidine, prevents release superoxide ion
CASE 2
CASE 3
nucleosomes are obstacle for transcription
methylation in non-divinding cells: make DNA more accessible for transcription-related
proteins
methylation in mitosis: opening chromatin structure for replication
chromatin: package genome in nucleus and gene expression regulation
histone genes don’t have introns
methylation histones > condensed/compact heterochromatin
nuclease digests linker DNA
acetylation: more open chromatin, less tight interaction DNA-nucleosome
DNA transposon: cut-paste
retrotransposon: copy-paste (RNA intermediate > DNA intermediate)
- integrase
DNA and histone methylation silences transposon transcription
epigenetic modifications: reversible, not transferred to offspring
epigenetics: changes in gene expression that don’t involve changes to underlying DNA seq
- change in phenotype without change in genotype
DNA methylation is often maintained over generations
detection DNA methylation: bisulphite sequencing (chemical conversion C>U) or methylation
sensitive restriction enzymes
detection histone modification: ChIP seq
detection small RNAs: deep sequencing
detection active transposons: transposon display
CASE 4
auxin recognized by (TIR1) receptor protein complex
receptor (E2) transfers Ub to substrate (= Aux/IAA)
poly-ubiquitylated Aux/IAA proteins is degraded by proteasome
ARF (auxin response factor) promotes transcription
- binds DNA as dimer at high affinity
,TPL (topless) inhibit transcription
mono-ubiquitylation: changing location or activity of proteins
acetylation: neutralizes charge DNA and histones > weakened bond
two-hybrid system: study protein-protein binding interactions (bait-prey)
disassortative: high degree nodes tend to attach to low degree nodes
robustness allows system to maintain functions against disruptions
coherent feed forward loop: indirect path has same sign as direct path
complementation: expression of multiple genes in pathway is necessary to obtain specific
function
gene interaction: genes at multiple loci determine single phenotype
epistasis: effect of one gene depends on effect of other gene
ChIP: determine TF binding sites in genome
CASE 5
Ames test to check mutagenic strength of carcinogens
- use plate without histidine to check for mutated DNA
ionizing radiation > doublestrand DNA breaks > deletions, duplications, inversions etc
aneuploidy: abnormal number chromosomes in cell
oncogene is mutated version of proto-oncogene
angiogenesis: new blood vessels formed
phosphorylation: serine, threonine, tyrosine
ubiquitilation: lysine (isopeptide bonds)
Fundamental genetics concepts
genetic terms:
gene = inherited factor which determines a characteristic
allele = one of more alternative forms of a gene; variant of sequence of nucleotides at
particular location/locus on DNA molecule
locus = specific place on the chromosome
genotype = set of alleles possessed by individual
phenotype / trait = appearance or manifestation of a characteristic
heterozygote = individual possessing two different alleles at the locus
homozygote = individual possessing two equal alleles at the locus
,one gene: one ORF; alternative splicing (→ different mRNAs)
post-transcriptional modification: RNA primary transcript is chemically altered following
transcription from gene to produce mature and functional RNA molecule that can then leave
the nucleus and perform any of a variety of different functions in the cell
genes confer phenotypes
regulatory elements: binding sites for transcription factors; involved in gene regulation
DNA > pre-mRNA > mRNA > polypeptide
startcodon: methionine
, genetic variation due to recombination
law of segregation: during gamete formation, the alleles for each gene segregate from each
other so that each gamete carries only one allele for each gene and offspring acquire one
allele from each parent
law of independent assortment: genes for different traits can segregate independently during
the formation of gametes and the laws of chance govern which particular characteristics of
the parental pairs will occur in each individual offspring, the principle of independent
assortment results from the independent separation of chromosomes during meiosis
