Topic 4b: the human genome Flashcards
What is the organization of our genome?
Our genome is organized by chromosomes, where each organism has a varying number of chromosomes. The human genome is encoded on both nuclear and mitochondrial chromosomes.
How is mitochondrial DNA inherited?
Mitochondrial DNA can only be inherited from the mother.
How is the Y chromosome inherited?
The Y chromosome can only be inherited from the father
What is the length of one turn of a double helix and the length of the whole genome in a single cell?
One turn of a double helix is 10.4 bp and 3.4 nm in length. The whole genome is about 2 meters long and is present in every single cell.
How is chromatin organized?
Chromatin is organized in nucleosomes, which are packed in a solenoid.
What regulates the folding of chromatin?
The folding of chromatin is regulated by “histone marks” such as DNA/histone methylation and acetylation.
How do chromosomes interact during transcription?
When areas are unwound for transcription, they can interact with each other, and this interaction can be inter- or intra-chromosomal.
What is the reference genome, and why is it biased?
The reference genome is a composite sample from many individuals and is used for normalization. It is biased because, initially, the individuals were all Caucasian, but this is now being fixed.
What are the components of a gene?
A gene contains a start and stop codon, a promoter, introns and exons (of varying lengths), and other regulatory sequences.
How is RNA similar to DNA, and what are the types of RNA?
RNA is similar to DNA, but there are many types, including coding (PolyA-mRNA and non-PolyA-mRNA) and non-coding RNA (structural: piRNA, telomeric, DNA repair, replisome, SnoRNA; ribosome-associated: rRNA; RNA-associated; regulatory: miRNA, TSS-associated, anti-sense, enhancer RNA).
Which chromosomes have more genes?
- Those with less genes, does not mean that they necessarily have less “information,”
- it maybe just has more relevant genes, meaning that if altered, it may have more important effects
what is Phased DNA?
variant data are ordered along one chromosome and so from these data you know the haplotype.
Unphased data are simply genotypes without regard to which one of the pair of chromosomes holds that allele.
what is Compound heterozygosity?
The presence of two deleterious variants located in the same gene but on different chromosome copies of an individual.
It is possible to distinguish between compound heterozygosity and the occurrence of two variants on the same chromosome copy by determining the haplotype phase.
What constitutes the largest portion of our genome?
The largest portion of our genome consists of repeat sequences, found between exons and different genes.
What are tandem repetitive sequences, and where are they found?
Tandem repetitive sequences are short sequences that repeat and are highly susceptible to polymorphisms. They are found in specific areas.
What are transposons, and what happens if they go wrong?
Transposons are coding elements, but most are mutated and don’t code for any functional protein. If a transposon inserts itself into an exon, it may cause disease.
How do transposable elements (TEs) affect the human genome?
Transposable elements affect the human genome by creating genes and RNAs, modifying regulatory networks, regulating gene expression and its repression, being a source of mutations, causing genome rearrangements, and affecting germline and soma.
What are topological domains in chromatin?
Chromatin is separated into heterochromatin (repressive chromatin) and euchromatin (open chromatin). In euchromatin, the chromatid is organized into topologically associating domains (TADs).
TADs include coding genes and many regulatory genes and proteins.
What is a single nucleotide polymorphism (SNP)?
An SNP is a single nucleotide change, the most common type of genetic variation among people, occurring once every 300 nucleotides on average.
with a difference of about 10 million nucleotides from person to person
How do SNPs within a gene or regulatory region affect the gene’s function?
SNPs within a gene or regulatory region may affect the gene’s function, predicting an individual’s response to drugs, susceptibility to environmental factors, risk of developing diseases, tracking inheritance of disease genes, and association with complex diseases.
What are rare variants, and how can they occur?
Rare variants can be inherited or occur de novo (new mutations).
What is a haplotype?
A haplotype is a set of DNA variations or polymorphisms that tend to be inherited together, either as a combination of alleles or a set of single nucleotide polymorphisms (SNPs) found on the same chromosome.
What are copy number variants (CNVs)?
CNVs are structural variants in our genome where there are different amount of copies of a specific gene, although most have no observable consequences since are generally mutually exclusive with coding regions (exons).
implication: depneding on which parent you inherit it from, you can have different number of genes present
How much of ASD heritability can be explained by common single-nucleotide polymorphisms (SNPs)?
10% of ASD heritability can be explained by considering all common SNPs.
What contributes to another significant part of ASD heritability?
Rare single-nucleotide variants (SNVs), insertions/deletions (indels), and copy-number variants (CNVs) affecting protein-coding regions.
What percentage of individuals with ASD have diagnostic gene-disruptive rare variants?
Around 10% of individuals with ASD have diagnostic gene-disruptive rare variants.
How do promoter de novo variants (DNVs) confer the risk of ASD?
Promoter DNVs, especially in evolutionarily conserved sequences, confer the risk of ASD by influencing multiple genes within the same topologically associating domain (TAD), resulting in overall dysregulation of ASD-associated genes.
What does the HapMap Project and the 1000 Genomes Project reveal about a typical genome?
A typical genome differs from the reference human genome at 4.1 million to 5.0 million sites, with >99.9% of variants consisting of SNPs and short indels, and structural variants affecting more bases.
What successful outcome resulted from using whole genome analysis in the NEI-sponsored Age-Related Eye Diseases Study?
A common variant in the complement factor H (CFH) gene (a gene that helps regulate inflammation in part of the immune system that attacks diseased and damaged cells) was identified as a risk factor for developing age-related macular degeneration (AMD).
how do you tell whether a change in our genome (e.g. SNP, CVN, …) has a function effect”
look at whether that gene is conserved across different species, and if it is, then the change probably have some functional importance.
with the HapMap project, which population was shown to be the most different from other population?
african
