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I was reading the Wikipedia articles about genome-wide association studies (GWAS) and whole exome sequencing.

As I understand, GWAS is used to identify most common SNPs that are proved to be associated with a disease/disorder. On the other hand there is an article about whole exome sequencing method where it said that it is more sensitive to identify Mendelian mutations in contrast with the SNP genotyping methods used in GWAS.

As the graph shows below, there is a distinction between Mendelian mutations and common mutations. What exactly does Mendelian mutation mean (why do we call it Mendelian)? What makes a Mendelian mutation so rare but effective in contrast with common mutations? Aren't common mutations inherited with the same rules as Mendelian ones?

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  • $\begingroup$ In short: Mendelian mutations are mutations where a single mutation causes a disease. An example would be the mutation that causes cystic fibrosis. Most diseases have more than one causative mutation (or in related genes of a pathway), so they are not seen as mendelian. $\endgroup$ – Chris Nov 2 '16 at 11:17
  • $\begingroup$ FYI: it's GWAS (genome-wide association study), not WGAS (wide genome association study). I'm not quite sure what a wide genome is. $\endgroup$ – MattDMo Nov 2 '16 at 20:54
  • $\begingroup$ Traits that depend on a single gene are often called Mendelian because they follow the classical patterns of inheritance that Gregor Mendel discovered in his studies of monogenic traits in pea plants. $\endgroup$ – leekaiinthesky Nov 2 '16 at 23:04
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I will focus more on the question of rarity, which the comments have not addressed. Recall that natural selection is operating on the human population. Because of this, bad mutations of large effect (disease mutations such as CFTR in your figure) are very rare, because selection is removing them at some rate from the population (people with cystic fibrosis are unfortunately very sick and are not as fertile as healthy people), whereas mutations with very little effect are not subject to much selection. Paper one and paper two are reviews describing the population genetics in more detail.

As suggested by commenters, Mendelian mutations are so named because they are single loci of large effect controlling traits (approximately). Common variants, by this logic, must have very little phenotypic effect, because they are not purged by natural selection (assuming that they are deleterious, or disease-causing).

Rule of thumb: 'Mendelian' alleles can easily be used to predict phenotypes (like disease) and are acted upon by natural selection. 'Common' alleles are individually not informative about phenotype and are thus mostly ignored by natural selection. Not exactly true, but close.

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