Theme 5, Module 4 Summary: Our Personal Genome

Appreciate the diversity of cell types produced by altering gene expression.
Identify genetic variation with no impact on cell function.
Understand that genetic variation may be useful under certain unusual conditions.
Recognize that we carry additional genetic diversity in our personal microbiomes.

Only about 2% of the approximately 3 billion base pairs of DNA in the human genome code for functional proteins or small regulatory RNA molecules.
Every human cell carries the same genome across 23 chromosome pairs.
Evolution has led to alternate alleles or variations of specific genes.
Individuals have two alleles of a gene, but there can be many alleles or different haplotypes in a population, leading to genetic variation.
Cell-type specific proteomes, resulting from gene expression, are important for vital cellular processes.

Cellular proteomes in multicellular organisms are driven by transcriptional programs that direct cells to specific functions.
Example: White blood cells migrate in blood vessels to monitor for infection and pathogens, while red blood cells carry oxygen to tissues.
Cells interact with each other through membrane-bound surface proteins.
Information programming cell functions is in our DNA, regulated across cell types.
Genetic variations influence cell differentiation and proliferation.
High fidelity is required for replication, transcription, and translation of functional proteins.
Alterations in proteins can change their shape and function, with broader implications.
Example: Sickle cell anemia is caused by a single nucleotide polymorphism that alters red blood cell shape, leading to anemia and pain.

Some genetic variations do not affect function, are asymptomatic, and contribute to diversity.
Example: ABO blood typing system. Red blood cells bind and carry oxygen the same way, but different blood types exist.
Transfusions of non-self blood types led to tragic consequences.
Blood type is a classification based on the presence or absence of specific inherited cell surface proteins or enzymes.

Blood type is reflected in inherited alleles in the ABO gene.
The ABO locus has three main alleles: A, B, and O.
A and B alleles code for glycosyltransferase enzymes that catalyze the formation of A or B agglutinogens on cell surfaces.
The O allele encodes an inactive glycosyltransferase.
The AB blood type has SNP polymorphisms, leading to slightly different transferases.
Alleles are inherited from parents, resulting in our specific blood type.

Some mutations causing changes in protein sequences can be beneficial under certain environmental conditions.
Example: HIV infection and CCR5 gene mutations.
HIV invades T cells by interacting with the CD4 receptor and CCR5 co-receptor.
Mutations in the CCR5 gene can provide immunity to HIV infection.
A 32 base pair deletion within the CCR5 gene shifts the reading frame, resulting in a partial and inactive CCR5 protein.
This mutation is prevalent in some populations.
One theory suggests that this mutation conferred resistance to the bubonic plague in European populations.
An alternate theory proposes selective pressure from smallpox led to the prevalence of this mutation.

There are 10 times as many bacterial cells in our bodies as human cells.
Bacteria are found on our skin, in our mouths, and in our digestive tracts.
Humans provide shelter and nutrients to these prokaryotic cells.
Bacteria in our microbiome are beneficial to our health.
Bacteria in the gut help digest food and produce essential vitamins.
Your personal collection of bacteria is different from others.
Microbiome diversity depends on exposure to different bacteria, antibiotics, and interaction with the environment.

The collection of bacterial species in our microbiome is diverse.
There may be over 3 million distinct genes across the species in our microbiome.
Humans have approximately 20,000 protein-coding genes.
This is a rich source of genetic diversity for adapting to a changing environment.
Scientists have studied variations in gut microbiomes in different regions.
Distinct mixtures of bacterial species are associated with America, Japan, and Europe.
Different populations have collections of genes that produce different vitamins and enzymes, affecting disease susceptibility.
Microbiome variation is associated with recent dietary patterns.
Diets high in animal proteins and fats are associated with a different microbiome population than diets high in plant-based sources.
The microbiome can respond rapidly to changes in diet, environment, and exposure to pathogens.

Our personal genome orchestrates the differentiation of diverse cell types.
There is genetic variation in populations that has no impact on cells.
Genetic variation may be neutral but beneficial under specific conditions.
Our personal genome is not alone; we carry additional genetic diversity in our personal microbiomes.