Genetics - is the study of genes and how they are inherited. In most cases, the genes we inherit are the exact copies that our parents have. Since each parent might have a slightly different version of each gene, the combination that happens when the two comes together can result in variations. So in another way, genetics is the study of inheritance and variations and how these genes work within the environment that it is in as compared to where it came from. That means, how the same genes worked in your parents versus how it works in you when these different forms of the same gene are combined. By the way, different forms of the same gene are called as an allele.

Mutation – in some cases a letter in the gene changes to a different letter. One way this can happen is when one gene is slightly different in one parent from the other (variation) as explained above. It can happen in other ways also. For example, if the letter A at position 100 in a gene is the normal letter at that position and then for some reason it changes to G, then that change is called a mutation. It may not create any problem but in most cases, a change from the normal letter to a different letter can cause problems. Then it is called a genetic disorder. Genetic disorders can be due to changes in one or many genes. If the disorder is due to changes in many genes, then it is referred to as a complex genetic disorder or a multi-gene disorder.

When a single change in a single gene causes a genetic disorder, then it is called a single gene disorder. Sometimes, this is also referred to as a Mendelian disorder. Examples are sickle cell anemia and Cystic Fibrosis. Several single gene disorders are also rare and are referred to as rare genetic disorders. More information on rare genetic disorders can be found here:

https://rarediseases.info.nih.gov/

Somatic and Germline Mutations: These are changes in the letters of DNA picked up in somatic cells. Somatic cells are the cells that make up most of our body except germ cells. Somatic mutations are also referred to sometime as acquired mutations. Germ cells are the egg cells (found in the female) and sperm cells found in the male. If a mutation happens in the germ cells, then they are called germline mutations. This can be passed on from parents to offspring. This is what leads to inherited disorders. Most mutations seen in cancers are somatic mutations. More information can be found here:

https://my.clevelandclinic.org/health/body/23067-somatic--germline-mutations

Inherited Disorders: When a genetic mutation is passed on from parents to children, then they are referred to as inherited disorders. What was referred to above as Mendelian disorders are all inherited disorders. This refers to Gregor Mendel, who is the father of modern genetics. He is the first one to observe and describe the inheritance of a genetic trait.

Let us learn a few more terms related to genetics. For example, if you want to know if you have sickle cell anemia (SCA), you do not really need to figure out if all of your HBB gene (hemoglobin B gene) has the expected DNA sequence and instead look at the exact location (or letter) where the sickle cell mutation is in the gene. Actually, the gene itself is 1600 base pairs long and the general neighborhood of that gene is around 3900 bp long. Instead, since the exact location of the sickle cell mutation has been known for a while (since 1957), all you have to do is to look to see if that position has the letter (base) A or the letter T. The technology used to read the base at that position (whether it is sequencing or DNA chips – essentially two different ways to do the same thing), will tell you if both copies are T or both are A or if one copy is A and the other is T. This is called your genotype at the sickle cell mutation position. If the letter is T in both copies of your gene (remember you have 2 pairs of every chromosome, one from each of your parent), you will have sickle cell anemia (SCA). Geneticists will say you are homozygous for that loci (locus is another word for position). In this case, both your parents would have contributed the same mutation, T, and that is why you have T in both copies. Geneticists have a term for different variations seen at a loci and that term is, allele. In this context, an allele can be defined as different forms of the same gene. In the sickle cell example, the T allele is homozygous. So, now you know what it means when someone says that “you are homozygous mutant in that position”. If you know what version of the allele is expected in a position, you can say it is the “mutant allele” or the “wild type allele”. In other words, if the letter at that position (or locus) is A in both copies, then you will have no sickle cell anemia (SCA). Geneticists will still say you are homozygous for that position, but homozygous wild type (that is the normal expected sequence in the “wild” or the general population). If one copy of your gene is A and the other is T, then you will not get the disease, but you are a “carrier” for the disease. In this case, you have both alleles and that is why you are a carrier. Another way to say this is to say that you are heterozygous for that position. As you can see, different terms can be used to essentially define the same thing and you can use those terms interchangeably. In the case of SCA, you can confirm all of this by looking at your red blood cells under a microscope. Now you are confirming your phenotype for SCA. It will show the expected sickle shape if you have the homozygous T allele, and that is how it was actually discovered. As you can imagine, if the homozygous A allele or the heterozygous A/T alleles were present, you will see a normal cell. Now you know some basic genetics and essentially how genomic technologies are used to give you information about your genome.

More information on basic genetics and about Gregor Mendel can be found here:

https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/

More information about Genetic Disorders can be found here:

https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders