4. Human Genome

Question 1

What is enhancer

Answer 1

DNA Sequence stimulating transcription

Composition and Location:
* regulatory sequences/elements of DNA. =Enhancers are part of the regulatory regions of genes.
* cis-elements: located on the same DNA strand as the gene they control.

Location:
Enhancers are part of the regulatory regions of genes. <-> promoters are located close to the transcriptional start site,

• enhancer sequences can reside up to hundreds of thousands of base pairs from the coding region. Enhancers are predominantly located upstream (5’) of the genes, but some elements may occur downstream (3’) or within the introns.
• They are also categorized among other intergenic sequences, along with promoters and silencers

Function:
* to facilitate transcription.

Mutations in enhancers can alter gene expression, potentially increasing or decreasing the amount of mRNA produced.
In viruses, enhancers are sequences that are involved in controlling events in virus replication.

Question 2

Human Genome Project (HGP)

Answer 2

a landmark international scientific research project that successfully determined, stored, and made publicly available the sequence of nearly all the genetic content of human chromosomes

Question 3

Human genome: raw version

Answer 3

The initial unrefined sequence produced by the HGP containing gaps and low-accuracy regions.
Which covered approximately 90% of the euchromatic (gene-rich) portion of the human genome and contained an initial analysis of the data.

Question 4

Human genome: full version

Answer 4

2004: 99% of human genome was analised acuratory.
(The Human Genome Project gave an almost complete map of all gene-containing regions, but some complex repetitive areas near centromeres and telomeres were missing)

Question 5

Human Variome Project

Answer 5

A global initiative to collect all human genetic sequence variations associated with disease.

Question 6

South Africa Project (Human genome diversity)

Answer 6

A project sequencing diverse African genomes to understand population genetics.

Question 7

Conservative genes

Answer 7

Genes that remain unchanged across evolution due to essential functions.
- metabolic enzymes, cytoskeleton
- regulatory genes: Hox genes, elements of signal transduction pathways

Question 8

One gene one enzyme hypothesis

Answer 8

the idea that each gene encodes a single enzyme. Today, we know that this idea is generally (but not exactly) correct.

Reasons：
* Some genes encode proteins that are not enzymes Enzymes are just one category of protein. There are many non-enzyme proteins in cells, and these proteins are also encoded by genes.
* Some genes encode a subunit of a protein, not a whole protein : In general, a gene encodes one polypeptide, meaning one chain of amino acids.
* Some proteins consist of several polypeptides from different genes. ** : Some genes don’t encode polypeptides. Some genes actually encode functional ** RNA molecules rather than polypeptides!

Question 9

One cistron one polypeptide hypothesis

Answer 9

Updated concept stating each gene (cistron) encodes one polypeptide chain.

Question 10

Genome annotation

Answer 10

the process of attaching biological information to sequences

• Structural Annotation : identification of sequence
• Localization of chromosome
• identifications of introns and exons,
• localization of regulatory regions
• Functional Annotation :
  Attachment of function to sequence
• biochemical
• other biological participation in regulatory and any interaction
• expression (when, in what cells, how much)

Question 11

Pseudogene

Answer 11

Non-functional gene copies resembling functional genes.

2types:
1. Intron-containing : chromosomal segment duplication -コピーにmutationで欠陥ができる
2. Intronless : reverse transcription, then reinsertion to genome

Functions:
1. In some cases regulation of the original gene by means of antisense interaction
2. Genetic junk

タンパク質を作ることはできない

元々遺伝子だったが、mutation/欠陥で機能を失ったDNA seq

Question 12

Gene fragment

Answer 12

Partial gene sequence lacking full coding capacity.

Question 13

Copy number variation (CNV)

Answer 13

Variation in the number of copies of specific DNA segments among individuals.

Question 14

LINE (Long Interspersed Nuclear Element)

Answer 14

Autonomous retrotransposons that can copy and insert themselves in the genome.

• 21% of human genome (850,000 copies)
• LINE-1: 17 % of them (500-1000 copies are functional)

Question 15

SINE (Short Interspersed Nuclear Element)

Answer 15

Non-autonomous retrotransposons that require LINE enzymes for movement.

• 13% of genome, 11% = Alu seq - non-protein coding seq.
• can cause breast cancer, ewing sarcoma, hemophilia

Question 16

Alu sequences

Answer 16

A type of primate-specific SINE about 300 bp long.

Question 17

MIR (Mammalian Interspersed Repeats)

Answer 17

Ancient SINE elements found in mammals that are no longer mobile.

Question 18

Retrogene

Answer 18

Gene copy created through reverse transcription of mRNA and genomic reintegration.

Question 19

Phenotypic complexity

Answer 19

The degree to which organismal traits are diverse and regulated by genetic and epigenetic factors.

Question 20

C-value paradox / C-value enigma

Answer 20

The lack of correlation between genome size (number) and organismal phenotype complexity.

Question 21

Theories about the role of non-coding DNA

Answer 21

Hypotheses suggesting non-coding DNA roles in regulation, chromatin structure, and evolution.

Question 22

How many percent differences between genomes of indivisuals?

Answer 22

0.5 %

Question 23

What are the percent of Coding sequence, Gene-related seqiences (including psudogenes, gene-fragments, introns, UTR) and intergenic sequences (Repetitive : transposons…)

Answer 23

Coding: 1.2 %
Gene related: 36 %
Intergenic : 62.8 %

Question 24

What is the ancestor of SINEs?

Answer 24

SRP RNA components
SRP: Ribonucleoprotein that recognize and targets specific proteins to ER and plasma membrane in eukaryotes

Question 25

**SVA elements**

Answer 25

- a family of non-autonomous retroelements within the primate lineage. - It has three main components,** SINE-R, VNTR and Alu.** - Over half of the SVA elements in primate genomes are full-length and they exhibit hallmarks of retroelements, indicating that they likely are mobilized in trans by target primed reverse transcription using the endonuclease and reverse transcriptase activities encoded by L1 elements. SVA elements are a relative newcomer to primate genomes. SVA elements have a variable copy number in the hominid lineage with about 2700 copies in the humans.

Question 26

What are the function of LINE-1

Answer 26

1. formation of intronless pseudogenes By its enzymes (reverse transcriptase, integrase, etc.) LINE-1 can convert a cellular mRNA to DNA which in turn integrates to the genome resulting the generation of intronless pseudogene. These genes are usually non-functional since they lack regulatory sequences. 2. **gene inactivation** A mobile element can be inserted to an internal position of a gene (to an exon or intron), which can cause the inactivation of the given gene. Insertion of the mobile element to an intron can result the generation of a stop codon by the alteration of splicing. In this case the protein can be truncated which does not necessarily lead to the complete abrogation of every protein function. 3. **transduction** 1) The poly A signal of LINE is weak  read-through to an adjacent gene exon 2) Insertion of a piece of LINE and the exon of the cellular gene „A” to gene „B” 3) Insertion of only the exon of cellular gene „A”, but not the LINE