12th lecture (genetics 1) Flashcards
how many base pairs are there in the human genome?
3 billion
how many genes are there in the genome?
25 thousand protein coding genes (1-2% of the genome)
how much of the genome is transcribed?
75-90% is transcribed (many regulatory RNA molecules = regulatory molecules)
what are some types of ncRNA (non-coding RNA)
miRNA lncRNA piRNA snoRNA tiRNA T-UCR TERRA
what is epigenetics?
regulation of genetic expression without altering the genetic code.
how can epigenetic regulation (altering gene expression with no change in the actual DNA)
via the use of micro-RNA molecules:
- 22 nucleotide long
- post-transcriptional regulation
what is the process for post-transcriptional regulation?
- miRNA gene (nucleus)
- Pre-miRNA
- pre-miRNA goes into the DICER complex, will form the single stranded mRNA.
- the single stranded RNA will bind to the RISC complex and then bind to target mRNA (messenger RNA) and prevents the translation of the mRNA or performs cleavage of that mRNA.
A given miRNA can silence multiple target genes, binding determined by the 3’ untranslated region sequence.
what was so significant about the miRNAs in terms of treatment?
cancers have certain miRNA patterns (microRNA) since some miRNA may be missing. (today this is not entirely true)
Targeting RNA interference can be used for therapeutic reasons.
describe the long non-coding RNAs?
the only difference between miRNA and lncRNA is their length; 200 nucleotide vs 100kb long RNAs Function: - regulate transcription, splicing - chromatin regulation - binding to histone proteins
they have been linked to various disorders
They also help inactivate one of the X-chromosomes.
name some of the disease that long non-coding RNAs (lncRNA).
XIST: X-chromosome inactivation
FMR4: fragile X-syndrome
BACE1: Alzheimer’s disease
what methods (in terms of epigenetics) are used to regulated DNA?
- DNA methylation: silencing DNA segments.
- Histone modifications (methylation and acetylation, Phosphorylation) They change the amount which the DNA code is accessible.
mutations in these regulation proteins can cause cancers as unnecessary proteins can be expressed without regulation.
what does it mean if a mutation is germline?
inherited and is transferred to offspring.
what does it mean if the mutation is somatic?
the mutation is no transferred to offspring.
name the types of protein coding mutation?
AA = amino acids
- missense mutation (one AA to another AA) such as sickle cell anemia, a Hg mutation.
- Nonsence mutation (a protein coding codon is converted to a STOP codon)
- Frameshift mutation: (insertion or deletion of a single nucleotide, altered reading frame)
- Trinucleotide repeat mutations (excessive number of trinucleotide repeats.
what are some types of mutation present at the nucleotide level?
Chromosomal aberrations that can be detected on a large scale.
- structural alterations: (deletion, amplifications, inversion, translocation)
- Numerical alterations (aneuploidy, monosomy, trisomy)
what are natural variations in the genome (polymorphisms)
SNP (single nucelotide polymorphism)
- There is about 99.5% similarity between 2 humans.
- potentially 15 million nucleotide differences
- 6 million known SNPs. (some can causes diseases) its hard to know how many of these could potentially cause harm. It could contribute to increases risk to other diseases.
what is the mendelian disorders?
a disease caused by a single gene.
what are some types of inheritance?
- Autosomal dominant
- Autosomal recessive (need to copies)
- X-linked
- Y-linked (not so common)
define the following:
- pleiotropy:
- Genetic heterogeneity:
- Modified genes:
- pleiotropy: single gene mutation with many phenotypic effects
- Genetic heterogeneity: mutation of different loci leading to the same bait
- Modified genes: at other loci.
Describe how an autosomal DOMINANT inheritance affects generations of a family?
- at least one parent affected
- manifested in heterozygous state (AA, Aa)
- Both males and females are affected
- 1:2 chance in the offspring to have the disease
- Delayed age of onset (huntington’s)
why are mutations to the receptors , transport proteins (regulators of metabolic processes, LDL rec) Almost always dominant?
Structural proteins are also affected. (collagen)
because the mutated receptor allele will repress the healthy normal allele and thus only the mutated allele will be present. Mutated regulatory proteins and alter the structure of the recessive allele.
50% reduction > symptoms > DOMINANT negative effect
why are enzymes rarely affected by autosomal dominant inheritance?
they are autosomal recessive.
because a mutated enzymes will be compensated by the other enzyme. The healthy allele will compensate for the lack of the mutated enzymes. Thus both alleles must be mutated to affect an enzymes.
Describe how an autosomal RECESSIVE inheritance affects generations of a family?
- Both alleles are mutated (aa)
- the disease can skip generations (parents may not be affected)
- offspring have 25% chance for having the disease.
- Enzymes are affected.
Describe how an X-linked inheritance affects generations of a family?
- heterozygous females (carriers) transmit to sons only)
- Affected males are hemizygous for the trait. (since they have only on X-chromosome)
- Rarely heterozygous females may be affected (x-inactivation)
- all daughters of an affected male will be carriers
- offspring of carrier females have a 50% chance for inheriting the mutated allele.
