EOFAD is a genetic disease, but it can sometimes be unclear what chromosomes, DNA, genes, and mutations really are or what autosomal dominance means.

Here, we dissect each of these terms and explain what they mean in the context of early onset familial Alzheimer’s disease. We thought it would be important to define and clarify important genetic terms often used in our community.

Introduction

Chromosomes are long threadlike strands that pack tightly into coiled structures to house our genetic material. Chromosomes carry our genetic material in the form of genes, which are stretches of DNA molecules. You can think of each chromosome as a package of DNA. Unlike genes and DNA, chromosomes can be visible under a microscope. Humans typically have 23 pairs of chromosomes, meaning 46 chromosomes in total, that they inherit from their parents. Each parent contributes half of the chromosomes to their child. Below is an image of a karyotype, or a zoomed in image of chromosomes, showing where the three EOFAD genes - amyloid precursor protein (APP), presenilin 1 (PS1 or PSEN1), or presenilin 2 (PS2 or PSEN2) - are located within a person’s chromosomes.

What are chromosomes?

Humans have ~20,000 genes spread throughout their 23 pairs of chromosomes. Each gene is responsible for providing the “instructions,” or code, that allows the body to function. If you imagine your entire genome (essentially all of your genetic material) as an instruction manual for your body, then chromosomes would be the chapters of that instruction manual, and genes would represent the “steps” in each chapter.

What are genes?

You may hear about scientists performing whole genome sequencing. This means that they look at a person’s entire genetic material or genome – all genes across all 23 pairs of chromosomes. You can think of your genome as the entire set of instruction manuals to create who you are.

What is a genome?

Early onset familial Alzheimer’s disease is caused when a disease-causing mutation is present in one of three genes: APP, PSEN1 or PSEN2. A mutation is a change in the DNA code of a gene. Using our instruction manual analogy, a mutation is like a spelling error in the instruction manual that ends up changing the meaning of the instruction itself. For example, the mutation PSEN2 N141I alters presenilin 2 protein (which is the protein coded by the PSEN2 gene) so it does not function properly. Some scientists and medical professionals, like genetic counselors, will sometimes refer to mutations as “pathogenic variants” and mutations that do not cause disease as “benign variants.” Here at Youngtimers, we use the term mutation. You can read why we chose to do this here .

What is a mutation?

The ways in which genetic conditions are passed down from generation to generation are called inheritance patterns. Knowing the inheritance pattern of a genetic disease helps family members determine their chances of inheriting the mutation/disease.

Each person typically has two copies of every gene, one on each chromosome. We inherit one copy of our genes from each parent. For some genetic diseases, inheriting one mutated gene from a parent is enough to develop the disease. Such diseases follow an autosomal dominant inheritance pattern. Someone who carries a mutated gene associated with an autosomal dominant genetic disease can pass on either their mutated copy or working copy of the gene to each of their children. For this reason, each of their children has a 50% chance of inheriting the mutated copy of the gene. In a family with an autosomal dominant disease, the disease is often seen in individuals over multiple generations, affecting a loved one in every generation.

EOFAD is a disease that follows an autosomal dominant inheritance pattern. People who inherit two normal and fully functioning copies of the EOFAD genes (APP, PSEN1, PSEN2) from their parents will not develop EOFAD.

On the other hand, people who inherit one non-working copy of an EOFAD gene (as in, a mutated APP, PSEN1, or PSEN2 gene), will be affected by EOFAD. Since it is an autosomal dominant disease, a person only needs to inherit one mutated copy of a gene to develop the disease. For this reason, the children of a person who carries a mutation in an EOFAD gene have a 50% chance of inheriting the EOFAD mutation.

It is important to note here that with each child, the slate gets wiped clean chances-wise, each and every child of a person who carries a mutation in an EOFAD gene will have a 50% chance of inheriting the mutation from the affected parent. An EOFAD mutation in a sibling does not affect the chances of another sibling inheriting the mutation.

What is autosomal dominant inheritance?

EOFAD 101: Genetics

An explanation of commonly used genetics terms in EOFAD

We talk about how genes code for certain things in our body, such as our eye color or blood type, however, to have a code, you need an alphabet and letters to write that instruction manual. That is where DNA comes in. In our analogy above, DNA serves as the letters used to describe the steps in the chapters of our instruction manual. DNA stands for Deoxyribonucleic Acid. There are four units of DNA, called nucleotides: adenine (A), thymine (T), cytosine (C) and guanine (G). Specialized machinery in our body can read different combinations of these nucleotides and begin creating protein, the building blocks of our bodies.

What is DNA?