G1- hitch hikers guide to human genome Flashcards
what is the replication of the human genome?
cell cycle and mitosis meisosis
what is the organisation of genes?
Promotors, start codons, introns and exons
What turns a gene into a protein?
Transcription, splicing and translation
post-translational modification and transport
what provides variation in the human genome?
Polymorphisms
Mutations
what contributes to disease?
- genes
- environment
what do genes control?
control predisposition to ALL common disease – eg. Caries, oral cancer
what is genetics being increasingly used for?
determine treatment
Describe the DNA structure.
• Strands of DNA pair up in an antiparallel fashion
• DNA is replicated and read
always in the 5’ –> 3’ direction
-bases are A,T, C, G
How is information in DNA held?
held in the sequence of the bases which are held on a sugar/phosphate backbone
what does the DNSA strand associate with?
associates with proteins (including histones) and is wound into a structure called a chomosome
What are the stages of the cell cycle?
M-mitosis G1- gap 1 Go-resting S-synthesis (DNA) G2-gap 2
Describe DNA damage and repair.
- DNA strand breaks
- Chemical crosslinking
- mismatched base
when does DNA replication happen?
during S phase
Describe key facts of DNA damage.
- DNA can be damaged during replication
- Repair mechanisms exist
- Defects in these repair mechanisms cause disease
What does mitosis produce from one diploid parent cell?
Two identical diploid daughter cells
what does meiosis produce from one diploid parent cell?
4 Haploid daughter cells
one of each chromosome to each cell
Describe crossing over at meiosis.
genes segregate independently, even if on the same chromosome
what does meiosis occur?
Occurs in gamete formation
what is different about RNA compared to DNA?
- Single stranded
- Ribose in backbone not deoxyribose
- Uracil (U) is used instead of Thymine (T)
what determines the amount of protein produced?
- Rate of transcription (manufacture of Pre-mRNA)
- Rate of splicing to mRNA
- Half life of mRNA
- Rate of processing of polypeptide
Describe the change from DNA to protein.
-DNA is transcribed to pre mRNA
-Pre mRNA is spliced to mRNA
-mRNA is translated to protein
3 bases encode 1 amino acid or a stop
-Protein is modified and moved round the cell
what causes sequence variations within a gene?
- Changes in the promotor sequence
- Changes in the exon sequence
- Ones that change an amino acid
- Sequence changes that do not
what causes sequence changes in the DNA between genes?
- Single Nucleotide polymorphisms (SNPs)
- Larger deletions or duplications
what are polymorphisms?
-Any variation in the human genome that has a population frequency of greater than 1%
or
-Any variation in the human genome that does not cause a disease in its own right. It may however, predispose to a common disease
what are mutations?
-A gene change that causes a genetic disorder. (a disease causing mutation)
Or
-Any heritable change in the human genome
why do variants of genome all segregate independently of each other?
because of crossing over at meiosis
what Is a genetic disease?
One caused by a change in the genes
Name some of these changes in gene?
Extra piece of chromosome Missing piece of chromosome Change in gene sequence Insertion or deletion of a few bases Change of a single base where it matters
what is the purpose of genome knowledge?
To know what a DNA test result means and use it for patient management
what does phenotype equal?
genotype + environment
what does all disease equal?
genes + environment
what is penetrance?
The likelihood of having a disease if you have a gene mutation
what does 100% penetrance mean?
you will always get the disease if you have the mutation
what are mendelian disorders?
-Diseases that segregate in families in the manner predicted by Mendel’s Laws
-Essentially a disease that is predominantly caused by a change in a single gene
(High penetrance)
what allows us to select one small pice of the human genome from a patient and amplify it?
Polymerase Chain Reaction (PCR) -make lots of copies of one short stretch of the genome
what results from promotor mutation?
- No, or reduced transcription
- No, or reduced protein
what results from splice consensus altered?
- mRNA decay
- Abnormal or absent protein
what results from a base change makes a new stop?
- mRNA decay]
- short or absent protein
what results from base change that alters amino acid sequence?
different or non-functioning protein
Name the types of mutation in DNA sequences.
- wild type
- stop
- missense
- insertion
- deletion (out of frame)
- deletion (in frame)
- triplet expansion
Can different mutations in the same gene cause the same disease?
Yes
what effect does different mutations have?
have different effects on the protein produced and these can be predicted
what is non-mendelian inheritance?
Everything else including common “multifactorial” diseases
why sometimes is a child affected but neither parent seems to be affected?
- New mutation occurs as genes transmitted to child
- Parent doesn’t show clinical features but carries mutation (non-penetrance)
- Parent carries mutation but has very mild disease (variable expressivity
what different outcomes can gene mutations have?
-Mutations can affect the same gene in different ways,
Leading to different disease processes
but
-Mutations in different genes can also cause the same
Disease
what is used to find out diagnosis?
- clinical history
- family history
- clinical examinations
- genetic tests
what can we do with diagnosis?
- recurrence risk
- treatment
- prognosis
- genetic tests
