General genetics Flashcards
define gene
is a DNA coding sequence for a protein or ribosomal RNA
give me a bulk idea of how the gene is comosep
- Initiation codon 2. ORF (open reading frame) 3. exons and intronsfollowiin the last exon is the 3’UTR - untranslated regio
what percentage of DNA is junk?
97%
what does junk DNA do?
nothing. does not code for proteins and does not code for RNAr it has SINE (short interspersed elements) LINE (long interspersed elements) mini and micro satellites
what is the most repetitive sequence of junk DNA?
Alu sequencew occures 500K in the human genome
Genes controls cell activity through 2 processes
- transcription (DNA gives rise to RNA) 2. translation (RNA directs protein synthesis)
what are the 4 transcription factors?
- HTH helix-turn-helix 2. zinc finger 3. leucine zipper 4. heliz-loop-helix (HLH
many eye diseases result from transcription factor mutations….give examples
PAX2 (colobomas, ON hypoplasia, renal hypoplasia) PAX3 Waardenburg syndrome) PAX6 aniridia, peters,dominant foveal hypoplasia)
tell me about intron excision
The purpose is to leave the chain only with EXONS the process of removing introns is called Splicing sliciing takes places in splisosomes Aprox 15% of point mutations are cause by splicing errors Splicing errors can cause RP
what is the name for the process of removing introns?
splicing
besides splicing is there anothewr way to remove introns?
yes, by Alternative splicing The produict of this are called ISOFORMS (instead of proteins)
what is imprinting?
is a process by which a gene is modified example of errors in imprinting are Prader-Willi and Angelman syndromes
what is DNA damage and repair?
-each cell looses 10K bases per day. -this DNA is damages by many factors such as temperature, UV light, chemicals, etc -the repair mechanism svaes the cells. - if the DNA can not be repaired a tumor occurs. - 80-90% of cancers are a results of damaged DNA - DNA rapair occurs excision and mismatch repair
what if DNA is damages and can not be repaired?
the cell becomes a tumor and gives cancer
what is a gene?
the unit of coding sequence for a protein
what is the gene structure?
- it has introns (not coding for proteins
- exons (code for proteins)
- starts with 5’
- has a Promoter
- then a transcription factor
- stop codon 5’ UTR
what % of DNA is JUNK?
97%
what is the most repetitive junuk sequence?
ALU sequence
what is the process to produce a protein?
- transcription *gives rise to RNA)
- splicing (remove introns)
- translation (luego viene el traductor tarde) RNA directs synthesis of proteins
what are the 4 transciption factors?
- HTH helox-turn helix
- HLH heliz loop heloz
- zinc finger
- leucine zipper
what are the ophthalmic diseases that result from transcription facvtos mutations?
the PAX family
- pax 2 = optic nerve coloboma and hypoplasia
- pax 3 = waardenburg syndrome
- pax 6 = aniridia, dominant foveal hypoplasia, Peters and AD keratitis
what is the name of the process to remove introns? and how is it done?
- its called splicing (RNA goes from full to only exons)
- takes place in spliceosomes
- errors in splicing can cause disease
- point mutations
- retinitis pigmentosa
what is alternative splicing?
- occurs during splicing
- process that creates multiple copies of RNA
- but some skip exons
- the product is called isoforms
- these isoforms are tissue specific
- an example of useful isoforms are in the cornea
- VEGF-1 receptor has a role in angiogenesis
- in the cornea the VEGF-1 isoforms anct as VEGF trap and keep the cornea avascular
what is the name of the process of X chromosome inactivation? and what is the purpose or significance?
- its called Lyonization (in honor to Mary Lyon)
- has importance in x-linked disease because affects the severity or phenotype of these diseases
- for example in x-linked RP
when looking at the pedigree, if MOST of the males are affected, what should you think?
its an x-linked disease
when looking at the pedigree, is the ration of male and female affected is 50/50, what should you think?
in an autosomal disease
is autosomal disease how can you tell it is dominant or recessive?
- if the parents do not have the disease it is RECESSIVE
- if one of the parents have the disease then its DOMINANT (but if only the mother passes the disease then it must be mitochondrial)
remember that on the pedigree you have to see males and females almost equally affected.
tell me key features of autosomal recessive inheritance
- parents unaffected
- skips generations
- offsping of two heterozygous has 25% chances of inheriting the disease
- more frequent in consanguinity
key features of autosomal dominant
- appears in both sexes
- one of the parents must have the disease
- offspring of affected has a 50% chance of inhering
- does not skip generations
- if the parent does not have the disease it could be a DE NOVO mutation
rules of x-linked Recessive
- father does not transmit to son
- classic, more males than females are affected
- a carrier mother has 50% chance to pass to her son
- trait skips generations
- all daughters of affected fathers are carriers
Basicamente el padre hipocrita. Porque nunca la pasa al hijo pero si le encarga a la hija a que le pase al nieto.
rules of x-linked dominant
- Father never passes to son
- both sexes affected but more females
- does not skip generations
- affected fathers PASS the DISEASE to all daughters
- affected mothers will pass the disease to 50% sons and 50% daughetrs
El papa machista.NUNCA se lo pasa al hijo pero si a la hija. La mama mas equitativa se los pasa a los dos.
rules of mitochondrial inheritance?
inherited from mother only
rules of -ylinked?
only males affected
passed from father to son
does not skip generations
ex: color blindness?
what is th emost likely inheritance pattern on this pedigree?
- X-linked recessive
- Hemophilia
- Only males are affected
- skips generations: RECESSIVE
inheritance pattern on this pedigree?
mitochondrial
if on a pedigree both sexes are affected what could it be?
AR
AD
x-linked DOMINANT
but no XLR because that is in males
what is the inheritance on this pedigree?
x-linked dominant
- both sexes
- does not skip generation (so no AR)
- father al queso pasa a las hijas
- madre justa pasa a los dos
what is the inheritance pattern on this pedigree?
autosomal recessive
- parents unaffected
- skips generations
- offsping of two heterozygous has 25% chances of inheriting the disease
- more frequent in consanguinity
what is the inheritance pattern?
autosomal dominant
- appears in both sexes
- one of the parents must have the disease
- offspring of affected has a 50% chance of inhering
- does not skip generations
- if the parent does not have the disease it could be a DE NOVO mutation
what is the inheritance pattern?
x-linked dominant
- father does not transmit to son
- classic, more males than females are affected
- a carrier mother has 50% chance to pass to her son
- trait skips generations
- all daughters of affected fathers are carriers
- Basicamente el padre hipocrita. Porque nunca la pasa al hijo pero si le encarga a la hija a que le pase al nieto.
what is the inheritance pattern?
mitochondrial
- passed by mother only
what is imprinting?
- is an epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner.
- if the allele is inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed
- If the allele from the mother is imprinted, then only the allele from the father is expressed.
- Forms of genomic imprinting have been demonstrated in fungi, plants and animals.[1][2] As of 2014, there are about 150 imprinted genes known in the mouse and about half that in humans
- example: Wims tumor
examples of diseases with abnormal DNA repair?
xeroderma pigmentosum
tricodermatophytosis
- what happens if there is no DNA repair?
- what are the 2 mechanisms of DNA repair?
- cancer tumors occur. 80-90% of tumors are cuased by deffects in DNA repair
- DNA repair done by
- excision repair
- mismatch repair
- basicaly done by antioncogene p53, also know as… THE GUARDIAN of the GENOME
- it senses if there is repair that can be done it starts repair but if its too much damage then causes cell apoptosis
what is the antioncogene p53 gene?
its the GENOME GUARDIAN
DNA repair done by
- excision repair
- mismatch repair
- basicaly done by antioncogene p53, also know as… THE GUARDIAN of the GENOME
- it senses if there is repair that can be done it starts repair but if its too much damage then causes cell apoptosis
what are the requisites to identify a mutation?
- the mutation does not occur in the normal population
- it produces a DNA mutation that alters the protein function and this correlaqtes with the phenotype
- the mutation cosegregates in the family according to inheritance pattern
what are all the types of mutations?
- Missense mutation substitution of one amino acid for another in the protein made by a gene. Creates a different protein
- Nonsense mutation Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein.
- Insertion An insertion changes the number of DNA bases in a gene by adding a piece of DNA.
- Deletion larger deletions can remove an entire gene or several neighboring genes.
- Duplication A duplication consists of a piece of DNA that is abnormally copied one or more times.
- Frameshift mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.
- Repeat expansion Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated.
how do you calla mutation that results in a gene WITHOUT and active product?
NULL mutation
Null mutaitons include
Missense mutation
is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
Nonsense mutation
Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
what ia a polymorphism?
a DNA variation that occurs in >1% of the population
name some tumor suppressor genes
- retinoblastoma
- NF1
- NF2
- tuberous sclerosis
- VHLD
what is a feature in mitochondrial diseases?
- disease worsens with age
- number of involved organs inicreases with time
*
name some mitochondrial diseases
- Kearn-sayre syndrome
- CPEO
- LHON
- maternal inherited sensorineural deafness
- adult-onset diabetes and deafness
- NARP (neuropathy, ataxia, RP)
- streptomycin suceptibility to ototoxicity
features of CPEO
- ptosis
- paralysis of EOM
- pigmentary retinopathy
features of Kearns-sayre syndrome
- ptosis
- EOM paralysis
- severe RP
- heart blocks
All this patients have LARGE DELETIONS!!!!
features of Leber hereditary optic neuropathy
- mitochondrial disease
- causes
- optic atrophy
- peripapillary microangiopathy
- more in males than females
- the trait not transmited to offspring of males PADRES BUENOS
- MADRES al queso. All daughters and sons of affected mothers will have the disease
- Its cause by one single change G to A
- at the nucleotide position 11778 in ND-4 gene
- ND-4 gene involved in NADH dehydrogenase synthesis
- nucleotide 3460 ND-1
- nucleotide 14484 ND-6 and 14459
- 12 other mutaitons but they may be variants
- at the nucleotide position 11778 in ND-4 gene
- THIS DISEASE causes severe vision loss
-
SOME CAN IMPROVE (recover vision)
- 14484 greates recovery
- 11778 worse recovery
what is the importance of finding the gene in LHON?
the type of gene is associated with chances of recovering vision
14484 greates recovery
11778 worse recovery
what is a nucleoside?
what is a nucleotide?
they are chemical compounds
- nucleoside: SUGAR + NB (purine or pyrimidine)
- nucleoTIDE: nucleoside + phosphate
which is the DNA backbone?
tje SUGA….
ribose or desoxiribose
what is the difference between a triplet and a codon?
they are similar terms
- 1 sugar + 1 NB = 1 nucleoside
- 1 nucloside + 1 phosphate = 1 NUCLEOTIDE
- 3 nuclotides = 1 triplet
- if the triplet encodes an aminoacid its called a codon
- so…. CODON is the functional name of a triplet
why is the genetic code degenerate?
how many aminoacids are there ?
how many codon combinations are possible?
- there are only 20 aminoacids!!!!
- there are 4 Nitrogenate bases
- there are 64 combinations available
- the code is degenerate because more than one codon codes for an AA
which is the START codon?
AUG
codes for Methionine
what is the definition of the genetic code?
set of rules by which information encoded within genetic material is translated into proteins
what are the metric units of DNA?
measured in base pairs (BP)
a base pair is the nucleotide
kilobases (1000 bases)
Mb megabases (million bases)
where is the DNA located in the cel?
in the nucleous
how many BP are there in the human genoma?
3.2 billion of bp x2
how many chromosome we have?
how many are autosomes?
home many sex chromosomes?
- 46 chromosomes
- 23 pairs
- 22 pair autosomes
- 1 pair autosomes
- 23 pairs
what percentage of a DNA is conserved?
what is the importance or meaning of DNA conservation?
- 5% of DNA is conserved across species
- this means that if we compare all the human genome to one of mice or nematodes there is 5% that is exactly equal
- this means that this 5% is extremely important for cell survival
what percentage is junk DNA?
- 30% but its not junk, we just don’t know what is the function yet.
- it may have to do with packaging, segregation, replication , etc
what percentage of DNA is protein coding?
1.5%
at least that is what we know.
80% might be functional
what is the ENCODE project?
The Encyclopedia of DNA Elements (ENCODE)
https://www.genome.gov/10005107/
- is a public research project launched by the US National Human Genome Research Institute (NHGRI)
- in September 2003.
- Intended as a follow-up to the Human Genome Project (Genomic Research),
- theENCODE project aims to identify all functional elements in the human genome.
*
what is a gene?
- its the UNIT of HEREDITY
- its a region of DNA that is transcribed
- transferred from parents to offspring
- determines the characteristics of the offspring
what does a gene produce?
what is the gene structure of components?
- produces: proteins, enzymes, signalling molecules
- a gene has:
- PROMOTER
- EXONS
- INTRONS
- STOP region
what is the average size of a gene
- average size is 20 KB
- an average of 8 exons ( 1 exon - hundreds of exons)
- There are 22,000 of genes
how many genes are there in the human genoma?
22,000 protein coding genes
what is splicing?
what is the translation to spanish?
- in Spanish is EMPALME
- is the EDITING of pre-RNA transcript
- with splicing, INTRONS ARE REMOVED and exons are ligated
