Sarah Margareta Ibrahim▯ Wednesday, January 9th 2013
BIOL 202 - Basic Genetics
Lecture 2 - Single Gene Inheritance I
Reading: Ch. 2 p. 27-46
Case 22-2007 NEJM
• A case published in the New England Journal of
• Woman with family history of gastric and breast
• Mild chronic GI symptoms (dyspepsia,
heartburn, and mid-abdominal discomfort)
began to increase in severity and frequency
over a few months
• Symptoms did not resolve with antacid therapy
• 5lb weight loss (attributed to stress)
• Endoscopic exam of upper GI tract few months
earlier was normal
• *Note about Gastric Cancer: second leading
cause of death in the world but is less common
in the west. Only 1 to 3% of the cases are
probably attributable to a high-penetrance
• Figure 1 is the pedigree of this woman (sheʼs
circled in red)
• When patientʼs maternal aunt was diagnosed
with cancer she took a test to detect mutations in the CDH1
gene which showed an R732Q mutation which resulted in
the substitution of glutamine for arginine at amino acid 732.
Patient took same test, had same mutation. Looking more
and more like itʼs associated to genes...
• CDH1 gene - codes for a transmembrane protein called E-
cadherin protein. They play a role in cell adhesion (bind
cells to one another)
• If you down-regulate this gene (in other words if you cause
this mutation), it allows cellular adhesion to fall apart so
cells can move around a lot more. So this can easily play a
role in the metastasis (spread) of cancer. This mutation is
• How to manage a disease like this? Prophylactic
gastrectomy (removal of the stomach) and would put tube
down stomach to ensure that everything was alright. But
since patient was hesitant, they did an upper endoscopy
with a methylene blue stain and no cancer was detected.
• If you have this mutation,the possibility of developing the cancer at some point in your life is
very high (around 80%-90%)
• Patient elected to perform a total gastrectomy - stomach was removed, connected back the
esophagus to the duodenum and a section of the small intestine was used as a pouch (a sort
of pseudo-stomach). Now the patient has no more stomach. This is a routine treatment. Eight
▯ 1 Sarah Margareta Ibrahim▯ Wednesday, January 9th 2013
days post-surgery, she was eating a normal, solid diet but these patients have to eat a little
less than normal people. But she gained weight.
• When pathologist looked at cross section of her stomach (see second ﬁgure on ﬁrst page), it
was discovered that she actually had cancer.
• Each of her children has a 50% chance of having the mutation: Mendelʼs Law of Equal
• Worked with peas in a garden - not humans
• Genetics prior to Mendel: Ancient Greeks believed that there was just a “blending inheritance”
or a “mixture of semen and menstrual blood”.
• But what does the male contribute? What does the female contribute? How could you have
two people with brown eyes and end up with a blue eyed kid?
• About Mendel: Farmerʼs son who grew up in the Czech Republic. Wanted to become a teacher
but failed out of school and became a monk -
monasteries were centers of learning.
• The person in charge of the monastery was
interested in genetics. The thing that was
important at that time was new kinds of crops
(age of curiosity) since there were all kinds of
discoveries being made and new biological
organisms cropping up as a result of exploration
in the west. So it was an important ﬁeld at the
• Mendel was then sent to the University of Vienna
where he learned a lot of math - he was a good
student. Wanted to help humanity by learning
more about inheritance.
• Why did Mendel work with garden peas? Monks
didnʼt want him messing with the animals. Also,
the peas were easier to control in terms of the
crosses. Controlled crosses are very important -
contaminated crosses are not good. In addition,
generations are short. The peas also produce
quite a large number of progeny. Furthermore,
the traits are easily discernible and there are a
lot of different varieties (different traits).
• If youʼre a geneticist, you need something that
shows very discrete variation (not a mixture of
things) - need something that is variable too.
Need varieties of peas that show enough
differences that you can actually do crosses that show inheritance.
• Mendel chose to study the inheritance of characters (phenotypes) whose is expression is
strongly inﬂuenced by gene action.
• These (peas, ﬂowers etc. with different traits) were commodities that you could obtain.
• Peas are also self-fertilizing so if you leave them alone for a while theyʼll fertilize themselves.
• These varieties existed as inbred lines (also called pure breeding lines) - meaning that all the
offspring will be identical to the parent. So if you have a yellow colored pea, they will only
produce a yellow offspring.
▯ 2 Sarah Margareta Ibrahim▯ Wednesday, January 9th 2013
Mendelʼs Results from the Pea Crosses
• So for one of his crosses (top left), Mendel has a pure breeding line of yellow peas which he
crosses with a pure breeding line of green peas. As a result, he obtained yellow. This was not
expected based on the prior “blended” theories. Why did the P produce a yellow F1? Before,
people would have assumed that it would have been a yellowish green pea. So somehow,
green went away.
• But in the F2 generation, thereʼs the reappearance of the