Notes Flashcards
Explain the concept of steric hindrance?
No free rotation around peptide bond.
C=O and N-H are in the same plane and the other 2 bonds in the peptide backbone can rotate.
This only allows for confirmations where the side chains don’t clash with the main chain.
How is DNA packaged?
Human genome consists of 3 x 10^9 base pairs of DNA with 23000 genes.
Nucleosomes are the lowest level of packaging and it causes 7 fold condensing of DNA - octamer wrapped by DNA in a left handed superhelix with linker DNA between histones.
Further packaging into 30nm fibre which creates 40 fold condensing of DNA.
In total, there is 10000 fold condensation.
How do enzymes work?
Substrate binds to active site, enzymes arrange substrates so bonds are strained via oxidation and reduction reactions.
Substrate is bent so it resembles the transition state - atoms rearranged geometrically and electronically so the reaction can proceed.
Replication fork proteins
Single strand DNA binding protein - prevents single stranded DNA from locally folding.
Sliding clamp - ensures DNA polymerase is in the correct place and prevents it from falling off.
DNA error frequency?
1 change per 10^9 base pairs.
Features of thalassemia?
Darkening of skin due to melanin overproduction and overstimulation.
Hemosiderosis (elevated iron absorption due to chronic anaemia).
Extramedullary haematopoiesis.
Hepatosplenomegaly/hepatomegaly.
Associated with endocrinopathies e.g. diabetes and thyroid disorders.
Gene knockdown
Decreasing amount of protein you get from a gene.
HDL vs LDL
HDL = good cholesterol, peripheral tissues to liver so lowers total serum cholesterol. LDL = bad cholesterol, prolonged levels leads to atherosclerosis, liver to peripheral tissues, 40% of weight made up of cholesteryl esters.
Cholesterol in its storage form?
Acylated at Carbon-3.
Wobble base?
3rd base in a codon is highly variable so it’s called the wobble base.
Types of intracellular transport
Gated transport - e.g. nuclear transport through nuclear pores.
Transport across membranes - e.g. importing newly synthesised proteins into ER.
Vesicular transport - e.g. inter-organellar transport.
Define the 7 types of congenital abnormalities
Malformation = primary structural defect, usually involves a single organ showing multifactorial inheritance. Disruption = secondary abnormal structure of an organ or tissue, caused by ischaemia/infection/trauma - not genetic although factors can predispose. Deformation = abnormal mechanical force distorting a structure, occurs late in pregnancy, has a good prognosis because the underlying structure is normal. Syndrome = consistent pattern of abnormalities with a specific underlying cause. Dysplasia = abnormal organisation of cells into tissue, caused by a single gene defect. Sequence = multiple abnormalities initiated by a primary factor. Association = non-random occurrence of abnormalities but the cause is typically unknown, e.g. VACTERL association.
Features of Patau and Edwards syndromes
Patau = holoprosencephaly, heart defects, mental retardation. Edwards = kidney malformation, digestive tract defects, heart defects, mental retardation.
Features of the genomic disorders
Di George syndrome = chromosome 22 TBX1 gene, most common microdeletion, cardiac abnormalities, thymic hypoplasia, hypocalcaemia.
Cri du Chat syndrome = microcephaly.
Charcot-Marie-Tooth disease Type 1A = microduplication of chromosome 17 PMP22 gene, muscle weakness, hypotonia, missing reflexes, foot deformities, lack of sensation in feet and arms.
What is Mendelian inheritance?
Process whereby individuals inherit and transmit to their offspring 1 out of 2 alleles present in homologous chromosomes.
Examples of autosomal dominant inheritance
Huntington’s Disease, Osteogenesis imperfecta, Familial hypercholesterolaemia, Achondroplasia.
Complications to simple Mendelian inheritance
Incomplete penetrance = symptoms not always present on individuals with the disease-causing mutation.
Variable expressivity = disease severity may vary between individuals with the same disease-causing mutation.
Phenocopy = same disease but different underlying cause.
Epistasis = interactions between disease gene mutations and other modifier genes can affect the phenotype.
Consanguinity = union between 2 individuals who are related as second cousins or closer.
How can cancer-causing agents affect oncogenes?
They can turn proto-oncogenes into activated oncogenes which override apoptosis.
Examples of pharmacogenomics
KRAs test for cetuximab with colorectal cancer (KRAs mutation means you’re less likely to respond).
EGFR test with gefitinib for non-small cell lung cancer (EGFR mutations means you’re more likely to respond).
Maternal serum screening markers
Serum unconjugated oestriol levels are used to assess Down’s risk.
Low alpha fetoprotein suggests Down’s, high alpha fetoprotein suggests neural tube defects.
