Genomes-L2-Repetitive DNA sequences and Mitochondrial genome

what has happened in human evolution nuclear genome? and what comes out of it?

• whole genome duplications

• rearrangement of chromosomes

• smaller DNA duplications

deletion or repeating to genomic sequences which can lead to adaptation- advantageous or disadvantageous

what are multi gene families? why did they rise and an example

they raised due to tandem duplication events- alpha and beta global gene families

genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes.

• chromosome 16 and 11

• beta on Ch 11 have 5 genes- gives rise to globs

how did different types of globs arise?

came from a single gene ancestor through subsequent gene duplications and mutations, leading to the diversification

• such as haemoglobin, myoglobin, neurgolbin and cytoglobin

how do gene families arise? and what gives rise to pseudogenes?

duplicated genes that are separated by rearranged across different chromosomes- by rearrangement or copies of cDNA are inserted

these inserted copies are pseudogenes if they don’t have regulatory sequences- non functional

how much of the human genome is repetitive? how are these identified? an example of repetitive sequence?

½ to 2/3 of the genome is copied sequenced

identified by the function and dispersal patterns

• transposable elements

what are transposable elements? an example?

a type of receptive sequence in DNA

• can move around genome and insert themselves- can alter structure and function

• can lead to mutagenesis- disrupt normal function of genes by inserting themselves

• L1- long interspersed element- cause haemophilia A

how can transposable elements be harmful? an example

• disrupt normal gene function by inserting into the coding regions, regulatory elements of genes, potentially leading to changes in gene expression or protein function.

• cause mutagenesis-L1 disrupts factor VIII- haemophilia

example of Transposable elects mutagenesis?

L1- inserts itself into the factor VIII gene- causes de novo case of haemophilia A

how can transposable elements be beneficial? an example

provide genetic material for evolution of new protein coding genes and non coding RNAs- for cellular function and survival

• Rag 1a dn Rag2- for immune system of vertebrates- cataylsase VDJ recombination

how did the mitochondria arise?

by endosymbiotic capture- lead to a usually beneficial relationship- 2.7b y/a

information about the mitochondria- what roles does it play, how its made? etc

• nuclear genome codes 1000 genes for mitochondrial proteins

• mitochondria has its own genome which is coded within nuclear gneome

• mitochondria- helps with ATP production, regulates apoptosis, calcium homeostasis and make reactive oxygen

• make 90% of cellular energy from the electron transport chain

discuss mitochondrial genome

mtDNA- 37 genes and 13 proteins, 22 tRNAs and 2 rRNA

• 37 genes for make enzyme complexes for oxidative phosphorylation for ATP

• different cell types have different amount of mtDNA copies- eggs have large amounts- make NADH

• 16,000bp

how mitochondrial DNA transcribed?

• 2 DNA strands- 1 heavy(G guanine) and 1 light(cytosine C)

• regulated by the D loop control region- have divergent promotors

difference between mitochondrial DNA and nuclear DNA

• mtDNA is inherited maternally and encodes 37 genes, while nuclear DNA contains the majority of genetic information in the form of thousands of genes.

• mtDNA is circular and resides within the mitochondria

• whereas nuclear DNA is linear and located in the cell nucleus.

• mitochondria DNA is from single lineage- MATERNAL

what is autosomal dominant and autosomal recessive? Examples?

• dominant- trait expressed with one copy- 50% of children affected- Huntingtons, retinal dgeneration- rhodopsin variants

• recessive- trait expressed only when two copies are present- 25% of children are affected- such as recessive EB- collagen 7A1, CYCSTIC FOBROSIS dELTA f508

what are mendelian diseases?

Mendelian diseases are genetic disorders caused by mutations in a single gene, f

what are X linked diseases

• X linked recessive- al females from affected males are carriers- only have 1 x gene to pass on-

•  therefore 50% of her male children will have the disease and 50% of female children will be carriers

what are the two types of mitochondria diseases?

primary diseases- are caused by defects- usually neurological and muscular phenotypes as they need more mitochondria

secondary- much greater numbers but are accumulations of mutations over time- ageing disorders such as Alzheimers

what is heteroplasmic? how does this affect mitochondrial diseases?

where both normal and mutant mitochondrial DNA mtDNA coexist in a single cell or individual

• threshold effect- a certain amount of mitochondrial mtDNA needs to be present to show a phenotypic effect

types of treatments for mitochondria diseases?

1. pronuclear transfer- nuclear DNA is transferred to donor zygote with healthy mitochondria after fertilisation

2. spindle transfer- before fertilisation

types of disease related genetic variants and their effects

• chromosomal abnormalities- structure/number is affected

• sub chromosomal changes- smaller types

• small scale DNA changes- 1 or multiple base changes in nuclear/mitochondrial genomes- silent-changes bp but protein is the same, missense- amino acid changes, nonsense- stop codon is added early or stop codon naturally is replaced by an amino acid

• intronic mutations

effects: non function proteins RNA, over/under expression of proteins and RNA, splicing defects

example of chromosomal abnormality disease

patau syndrome- some cells of the body have extra genetic material from chromosome 13

• causes defects

trisomy 18

• extra chrosome at chromosome 18

• causing numerous developmental and intellectual disabilities.

consequences of point mutations in DNA

• point mutation for blood clotting in Factor VIII- haemophila- uncontrolled bleeding

• if it controls cell division- mutation can cause unctrolled dividing0 cancer

• if it controls DNA repair- mutation may not fix DNA properly- such as BRAC1 and BRAC2- leading to breast cancer

cystic fibrosis- dominant/recessive? what is the mutation etc

• recessive

• 1/25 people carry it

• deletion of 3 bases- phenylalanine position 508- delta f508