Source: Molecular Biology I, University of Central Florida, Chapter 1
Tags: genetic code, codons, SNV, SNP, alleles, genotype, bi-allelic, genomic imprinting, epigenetics, CpG, locus, housekeeping genes, beta-actin, GAPDH, hepatic cells, sickle cell, rs334, BIOL 101
Difficulty: Intermediate Prerequisites: Parts 1 and 2 of these notes (DNA structure, base pairing, transcription, translation, Central Dogma). You need to understand codons and how mRNA is read before this section will make full sense.
Once you know that DNA encodes protein via the Central Dogma, the next question is: how does variation in that code create differences between individuals? This section covers the genetic code itself (how codons map to amino acids), the types of genetic variation at the single-nucleotide level, and epigenetics, the layer of gene regulation that sits on top of the DNA sequence without changing it. You will also meet housekeeping genes and genomic imprinting. This material bridges molecular structure (Parts 1–2) and the genetics and gene regulation topics that follow later in the course.
The genetic code is a triplet code: three-nucleotide codons in mRNA specify amino acids. Variation at single nucleotide positions (SNVs and SNPs) accounts for much of the genetic diversity in human populations. Epigenetic mechanisms, such as CpG methylation and genomic imprinting, regulate gene expression without altering the DNA sequence itself. Some genes (housekeeping genes) are expressed in every cell type because they are essential for basic cellular functions.
Genetic code
The set of rules by which three-nucleotide sequences (codons) in mRNA specify amino acids during translation. The code is nearly universal across life. In simple terms, it is the dictionary that converts the four-letter alphabet of DNA/RNA into the twenty-letter alphabet of proteins.
Codon
A sequence of three nucleotides in mRNA that codes for a specific amino acid or a stop signal. There are 64 possible codons.
SNV (single nucleotide variant)
A position in the genome where one nucleotide is replaced by another. SNVs can occur anywhere in the genome. 99.679% of SNVs are bi-allelic (only two possible versions at that position). Think of it as a single-letter typo in the genome.
SNP (single nucleotide polymorphism)
An SNV where the less common version (minor allele) occurs at a frequency greater than 1% in the population. More than 96% of SNVs qualify as SNPs. In simple terms, an SNP is a common single-letter variant, not a rare one.
Bi-allelic
Having exactly two alleles (versions) at a given genetic position. Most SNVs are bi-allelic.
Alleles
Different forms of a gene. In a diploid cell (the standard for human somatic cells), there are two copies of each single-copied gene, one inherited from each parent.
Locus
The specific physical location of a gene on a chromosome.
Genotype
The combination of alleles an individual carries at a particular locus. For a bi-allelic site with variants T and C, the possible genotypes are T/T (homozygous), T/C (heterozygous), and C/C (homozygous).
Single-copied gene
A gene that exists at only one locus in the genome, with no duplicated copy elsewhere.
Genomic imprinting
A form of epigenetic regulation where the phenotype depends on whether an allele was inherited from the mother or the father. Only one parental copy is expressed (mono-allelic expression). In simple terms, the cell "remembers" which parent a gene copy came from and silences one of them accordingly.
Epigenetics
The study of heritable changes in gene expression that occur without any change to the underlying DNA sequence. Mechanisms include DNA methylation and histone modification.
CpG dinucleotide
A cytosine followed by a guanine in the DNA sequence (the "p" denotes the phosphodiester bond between them). CpG sites are common targets for methylation, a key epigenetic modification.
Housekeeping genes
Genes that are expressed in all cell types because they are essential for basic cellular functions. Examples include beta-actin and GAPDH (glyceraldehyde 3-phosphate dehydrogenase).
Beta-actin and GAPDH
Two classic housekeeping genes. They produce mRNA that is translated into proteins required for fundamental cell processes. Because their expression is relatively constant across cell types, they are commonly used as reference (control) genes in experiments.
Hepatic cells
Liver cells. Responsible for metabolism, detoxification, and the production of important proteins such as enzymes and hormones. A good example of specialised cells that express tissue-specific genes in addition to housekeeping genes.
SNP rs334
A well-known SNP in the beta-globin gene where an A-to-T change causes the sickle cell trait. One of the most studied examples of how a single nucleotide change can have a major phenotypic effect.
The code is a triplet code: each codon consists of three nucleotides in mRNA
There are 64 possible codons (4^3), coding for 20 amino acids plus stop signals
The code is degenerate (redundant): most amino acids are specified by more than one codon
The code is nearly universal across all forms of life
The codon table is organised by first, second, and third base position
SNVs are positions where a single nucleotide differs between individuals or between an individual and a reference genome
Can occur anywhere in the genome (coding regions, introns, intergenic regions)
99.679% are bi-allelic
SNPs are the subset of SNVs where the minor allele frequency exceeds 1%
More than 96% of SNVs meet this threshold
SNPs are the most common form of genetic variation in humans
For a bi-allelic SNP with alleles T and C, the three possible genotypes in a diploid organism are:
T/T (homozygous for T)
T/C (heterozygous)
C/C (homozygous for C)
An allele is one version of a gene
A locus is the position of a gene on a chromosome
Diploid cells carry two alleles per locus (one from each parent)
A single-copied gene has no duplicate at another locus
Human rRNA genes are an exception: they are duplicated and clustered on chromosomes 13, 14, 15, 21, and 22
Epigenetic regulation modifies gene expression without changing the DNA sequence
A major mechanism is chemical modification (typically methylation) of CpG dinucleotides
Genomic imprinting is a specific type of epigenetic regulation:
Expression depends on the parental origin of the allele
Only one copy is transcribed (mono-allelic expression)
This means the phenotype can differ depending on whether a given allele came from the mother or the father
Housekeeping genes (e.g. beta-actin, GAPDH) are expressed constitutively in all cell types
They encode proteins needed for basic cellular functions (cytoskeleton, metabolism)
Their stable expression makes them useful as experimental controls
Specialised cells like hepatic (liver) cells express additional tissue-specific genes on top of the housekeeping set, enabling functions like detoxification and hormone production
Located in the beta-globin gene
Involves a single A-to-T nucleotide change
This change alters the amino acid from glutamic acid to valine, causing haemoglobin S
Heterozygous carriers (one copy) have sickle cell trait; homozygous individuals (two copies) have sickle cell disease
One of the clearest examples of a single nucleotide change causing a major clinical phenotype
SNP genotyping is the basis for consumer genetic tests (like ancestry and health-risk panels) and for genome-wide association studies (GWAS) that identify genetic risk factors for diseases. The sickle cell SNP (rs334) is a textbook example of balancing selection: carriers are protected against malaria, which is why the allele persists at high frequency in populations from malaria-endemic regions. Epigenetic research is driving new approaches to cancer treatment, since abnormal methylation patterns are a hallmark of many tumours.
Students often confuse SNVs and SNPs. Every SNP is an SNV, but not every SNV is an SNP. The difference is frequency: SNPs have a minor allele frequency above 1%.
"Bi-allelic" does not mean an individual has two different alleles. It means there are only two possible versions at that position across the population. An individual can be homozygous (same allele on both chromosomes) or heterozygous (different alleles).
Epigenetics does not involve any change to the DNA sequence. Students sometimes conflate epigenetic modification with mutation. Methylation of a CpG site changes gene expression, not the sequence of bases.
Genomic imprinting is not the same as X-inactivation, though both involve silencing one copy. Imprinting is parent-of-origin dependent; X-inactivation is random.
⚠️ Know the distinction between SNV and SNP (frequency threshold of 1%).
⚠️ Be able to list the possible genotypes for a bi-allelic locus (e.g. T/T, T/C, C/C).
⚠️ Understand what epigenetics means: changes in expression without changes in DNA sequence. CpG methylation is the example to know.
⚠️ Genomic imprinting and mono-allelic expression are commonly tested. Know that it depends on parental origin.
⚠️ SNP rs334 (sickle cell, beta-globin, A to T) is a classic exam example.
⚠️ Know what housekeeping genes are and be able to name two examples (beta-actin, GAPDH).
True or False: All SNVs are SNPs.
Fill in the blank: A bi-allelic locus with alleles A and G has ___ possible genotypes in a diploid organism.
True or False: Epigenetic changes involve alterations to the DNA sequence.
Fill in the blank: In genomic imprinting, only the allele from ___ parent is expressed (answer: one specific parent, either maternal or paternal, depending on the gene).
True or False: GAPDH is a tissue-specific gene expressed only in liver cells.
Answers: 1. False (only SNVs with minor allele frequency above 1% are SNPs). 2. Three (A/A, A/G, G/G). 3. False (epigenetic changes modify expression without changing the sequence). 4. One specific parent (maternal or paternal, depending on the imprinted gene). 5. False (GAPDH is a housekeeping gene expressed in all cell types).
Q: What is the difference between an SNV and an SNP?
A: An SNV (single nucleotide variant) is any position where one nucleotide is replaced by another. An SNP (single nucleotide polymorphism) is a specific subset of SNVs where the minor allele frequency in the population exceeds 1%. More than 96% of SNVs qualify as SNPs.
Q: Explain genomic imprinting and how it differs from standard Mendelian inheritance.
A: In standard Mendelian inheritance, both alleles at a locus can be expressed, and the phenotype depends on dominance relationships. In genomic imprinting, only one allele is expressed based on which parent it was inherited from (mono-allelic expression). The silenced allele is epigenetically marked, not mutated.
Q: Why are housekeeping genes useful as controls in gene expression experiments?
A: Housekeeping genes like beta-actin and GAPDH are expressed at relatively stable levels in all cell types. This makes them useful as internal reference points: if you are measuring how much a gene of interest is expressed, you compare it to a housekeeping gene to normalise for differences in the total amount of RNA between samples.
Q: Describe the molecular basis of sickle cell disease at the nucleotide level.
A: SNP rs334 in the beta-globin gene involves a single A-to-T change. This converts a glutamic acid codon to a valine codon, producing haemoglobin S. In homozygous individuals, the abnormal haemoglobin causes red blood cells to adopt a sickle shape under low-oxygen conditions, leading to sickle cell disease.
Q: What is epigenetic regulation at CpG dinucleotides, and why is the "p" in CpG important?
A: CpG refers to a cytosine followed by a guanine in the same DNA strand, linked by a phosphodiester bond (denoted by "p"). Methylation of the cytosine at CpG sites is a major epigenetic mechanism that can silence gene expression. The "p" distinguishes this linear sequence from a C-G base pair across two strands.
SNVs and SNPs connect forward to population genetics and GWAS studies. Epigenetics, particularly CpG methylation and genomic imprinting, links to gene regulation and developmental biology chapters. The genetic code and codon table are prerequisite knowledge for studying mutations (missense, nonsense, silent) in later chapters. Housekeeping genes will reappear when you study experimental techniques like qPCR and Western blotting, where they serve as loading controls.
genetic code, codon, codon table, triplet code, degeneracy, SNV, single nucleotide variant, SNP, single nucleotide polymorphism, bi-allelic, allele, locus, genotype, homozygous, heterozygous, diploid, single-copied gene, genomic imprinting, mono-allelic expression, epigenetics, epigenetic regulation, CpG dinucleotide, DNA methylation, housekeeping genes, beta-actin, GAPDH, hepatic cells, liver cells, SNP rs334, sickle cell, beta-globin, haemoglobin S, molecular biology, BIOL 101