Learning Outcomes - Week 3 - The Human Genome Beyond Genes Flashcards
Describe The Human Genome (and its complexity)
The human genome is a complete set of nucleic acid sequences.
The human genome includes the coding regions of DNA, which encode all the genes (between 20,000 and 25,000) of the human organism, as well as the noncoding regions of DNA, which do not encode any genes
Understand the relative proportions of coding and noncoding regions in the
human genome
1.5% exons (coding) and the rest is non-coding!
Repeated DNA sequences: what are the different types? Explain them each
These repeats are found in various organisms. In humans, there may be over two-thirds of repetitive DNA in the genome. There are three major types of repeated sequences:
(1) terminal repeats: The genome includes long terminal repeats at either end that play a vital role in initiating DNA synthesis and regulating transcription of the viral genes.
(2) tandem repeats: A tandem repeat is a sequence of two or more DNA bases that is repeated numerous times in a head-to-tail manner on a chromosome. Tandem repeats are generally present in non-coding DNA.
(3) interspersed repeats: Interspersed repeats are usually copies of transposition elements, with ability to get reproduced and copies inserted at other places in the genome. These transposon elements can be either autonomous or non autonomous
Understand the differences in tandem vs interspersed repetitive elements
(1) tandem repeats: A tandem repeat is a sequence of two or more DNA bases that is repeated numerous times in a head-to-tail manner on a chromosome. Tandem repeats are generally present in non-coding DNA.
(2) interspersed repeats: Interspersed repeats are usually copies of transposition elements, with ability to get reproduced and copies inserted at other places in the genome. These transposon elements can be either autonomous or non autonomous
Differentiative between satellite, minisatellite and microsatellite elements,
including their repeat lengths
1) Satelite DNA (satDNA):
- Large tandem arrays of highly repetitive non-coding short sequences.
Array length
- 100s kb in length (1kb = 1000 bps)
Repeat length varies
- Range: 5 – 200 bp
Found in heterochromatin (structural)
- Centromeric and telomeric, some
interstitial
- Nucleotide repeats often well conserved
across species (difference is in how many repeats)
2) minisatelite DNA:
Array length
- Between 100-20,000 bp
- Repeat unit: 10 – 60 bp
- >1000 locations in the HG
- High mutation rate and diversity in population
Two types
- Telomere DNA repeats (TTAGGG) – 10-15 kb
- Ends of chromosomes
- Stop fraying of ends
- Loss through aging, stress
- Hypervariable minisatellites (VNTRs)
- Short blocks of tandemly repeated DNA
sequences dispersed throughout chromosomes
- Repeat unit length usually 9 – 64 bp
- L15440 (IGF2) has minisatellite DNA
- Nt 3401 – nt 3884
- Repeat number linked to diabetes, obesity
and polycystic ovary syndrome
3) Microsatelite DNA:
Array length
- Short blocks (<100 bp)
- Dispersed throughout chromosomes
Repeat unit usually 1 – 6 bp
- CA, CT, CAG – di, tri- & tetranucleotides
- Seen as 5’ – CACACACACACACACACACACA – 3’ in sequence
Used in identity testing as repeat length is hypermutable at certain loci
- Inherited differences in number of repeats at locus between individuals
- Number of repeats usually less than 50 (self-regulating)
Can be involved in disease states
- Higher mutation rate than other areas of DNA (i.e., genetic diversity)
- Expansion of CAG triplet in genes leads to Poly-Q diseases (insertion of Gln residues)
- Expansion of CGG triplet in gene leads to Fragile X disorders
- QUT: Expansion of TG in noncoding gene involved in prostate cancer progression
Microsatellite use in forensic/identity testing
Forensic/identity testing
* Pattern of fragment lengths viewed by gel electrophoresis
* Now capillary electrophoresis
* Can exclude or include individuals
Be able to describe the mechanism of repeat expansion
Be able to describe some diseases relating to DNA repeats
(Image below with additional answer)
- Fragile X Disease (FXS) phenotypes
* Affects males more severely
* (onset = puberty)
* Prominent or long ears and face
* Delayed speech & motor activities
* Autistic-like behaviours
* Hyperactivity
* Impaired social development
* Macro-orchidism (large testes)
* Females do not display severe symptoms
* ½ affected show symptoms
* Of these, only ½ show intellectual
disability
* Shy and quiet rather than autistic
(social anxiety) - (See image for 2 and 3 examples)
Understand and describe the pathophysiology of Fragile X disorders
X-linked inheritance
* Father’s X passed to daughters (Y to sons)
* Mother’s X passed to sons & daughters
Non-coding genes - what are they?
Examples of specialized RNA molecules produced from noncoding DNA include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which help assemble protein building blocks (amino acids) into a chain that forms a protein; microRNAs (miRNAs), which are short lengths of RNA that block the process of protein production
(See image for additional info)
How do long noncoding RNAs differ from small noncoding RNAs in size and
function
Long:
Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways
Short:
Small non-coding RNAs (sncRNAs) play critical roles in multiple regulatory processes, including transcription, post-transcription, and translation. Emerging evidence reveals the critical roles of sncRNAs in cancer development and their potential role as biomarkers and/or therapeutic targets
What are Transposons
Differences and commonalities between DNA transposons (Class 2) and
Retrotransposons (Class 1) and molecular basis for transposition
(Commonalities here)
- Transpose by:
- Class 2 by DNA intermediate.
- Class 1 by RNA intermediate - Element regarding the original site?
- Class 2: element missing from the original site
- class 1: element still at original site
Describe the LTR and non-LTR retrotransposons
What is the Difference Between LTR and Non-LTR Retrotransposons? LTR retrotransposons have long terminal repeats in their structure, while non-LTR retrotransposons lack long terminal repeats in their structure. Thus, this is the key difference between LTR and non-LTR retrotransposons
a, c
Microsatellite use in forensic/identity testing - what is the basics of the process?
Molecular basis for transposition of DNA transposons (Class 2) How do they jump?
Molecular basis for transposition of Retrotransposons (Class 1) How do they jump?
Retrotransposons (Class 1)
What do they look like?
How many types are there?
Are they very different in structure?
List the properties of transposons
