During which stage of human development does the role of epigenetics have the 

greatest impact on the development of epigenetic abnormalities?

(a) Infancy

(b) Puberty

(c) In utero

(d) Middle age

(c) In utero

Genomic imprinting is best described as:

(A) Epigenetic modifications caused by environmental factors

(B) The heritable transmission to future generations of epigenetic modifications

(C) Genes are silenced depending on which parent transmits them

(D) Phenotype is the same whether a given allele is inherited from the mother or 

the father

C) Genes are silenced depending on which parent transmits them

What is epigenetics?

The study of heritable changes in gene expression or phenotype casued by 

mechanisms other than changes in DNA sequences.

DNA methylation

The attachment of a methyl group to a cytosine base is followed by a guanine 

base...causes a gene to become transcriptionally inactive or silent.

Epigenetic processes play a major role in cancer initiation, progression, and 

treatment. Evidence: 20% of people with no inherited form of renal cell carcinoma 

(RCC) did not have a mutation but rather genes were silenced by epigenetic 

hypermethylation.

Histone modification

Adding chemical modifications to proteins called histones that are involved in 

packaging DNA

Micro-ribonucleic acids (miRNAs or miRs)

RNAs that are coded by short DNA sequences that can regulate gene expression 

networks.

Prader-Willi Syndrome

Deletion of 4 million base pairs of the long arm of chromosome 15; paternally 

inherited. Features: short statue, hypotonia, small hands and feet, obesity, mild to 

moderate mental retardation, and hypogonadism. 1 in 15,000 live births.

Angelman Syndrome

Deletion of 4 million base pairs of the long arm of chromosome 15, maternally 

inherited. Features: severe mental retardation, seizures, and an ataxic gate. Q1 in 

15,000 live births.

MLH1 & Colon Cancer

Major cause of one form of colon cancer (hereditary nonpolyposis colorectal 

cancer [HNPCC] or Lynch syndrome) when the methylation of the promoter 

region of the gene occurs. The protein product of this gene repairs damage to 

DNA. When this gene becomes inactive, damaged DNA accumulates, eventually 

resulting in colon tumors.

Inflammation & Cancer

Inflammatory and immune response may create a local environment in which cells 

can develop into a malignant phenotype and may even benefit progression and 

spread of malignancies. Chronic inflammation has been recognized for close to 

150 years as being an important factor, even predisposing us to the development of 

cancer. Some organs are more susceptible to cancer than others: GI tract, prostate, 

thyroid gland, pancreas, urinary bladder, pleura, and skin.

Both cancer and inflammation elicit inflammatory cells including neutrophils, 

lymphocytes, and macrophages to migrate to the site of injury and release 

cytokines and growth factors that stimulate local cell proliferation and new blood 

vessel growth to promote wound healing by tissue remodeling. Chronic 

inflammation means continued proliferation of the previous inflammatory 

response.

Successful tumors appear capable of manipulating cells of the inflammatory and 

immune response towards the phenotypes associated with wound healing and 

tissue regeneration, which is a process that includes induction of cellular 

proliferation, neovascularization, and local immune suppression. These activities 

benefit cancer progression, as well as increase resistance to chemotherapeutic 

agents.

Reactive oxygen species (ROS)

Promote mutations and block the cellular response to DNA damage

COX-2

Generates prostaglandins during acute inflammation. Associated with colon and 

some other cancers. Long-term high-dose use of NSAIDSs than inhibit COX-2 can 

reduce the risk of colon cancer by as much as 20%.

H. pylori & Gastric Cancer

Chronic infection with H. Pylori is an important cause of peptic ulcer disease and 

is strongly associated with gastric carcinoma, a leading cause of cancer deaths 

worldwide. Other cancers include gastric adenocarcinoma, and MALT lymphomas. 

H. pylori can also directly and indirectly produce genetic and epigenetic changes in 

infected stomachs. Mutations in p53 and methylation of specific genes.

Epigenetics & Cancer

Preventing epigenetic factors can theoretically prevent cancer. The interface of 

environment and genetics is chronic inflammation. Inflammation has been linked 

with increased DNA methylation, an epigenetic alteration.

Hemolytic Disease of the Newborn (HDN)

An acquired congenital hemolytic anemia, an alloimmune disorder in which 

maternal blood and fetal blood are antigenically incompatible, causing the mother's 

immune system to produce antibodies against fetal erythrocytes.

Alloimmunity

(sometimes called isoimmunity) is an immune response to nonself antigens from 

members of the same species

Iron Deficiency Anemia

Most common blood disorder in infancy and childhood, especially between 6 

months to 2 years. Not related to gender or race, but socioeconomic factors are 

important because they affect nutrition

RH Factor

If Mom is Rh-negative and baby is positive, whenever there is a mixing of 

maternal and fetal blood (particularly at birth when the placenta detaches and the 

mother is exposed to fetal blood) the mother's body will create anti-Rh antibodies 

which affects subsequent pregnancies. However, the capacity of the mother's 

immune system to produce anti-Rh antibodies depends on many factors, including 

her genetic capacity to make antibodies against the Rh antigen D, the amount of 

fetal-to-maternal bleeding, and the occurrence of any bleeding earlier in the 

pregnancy.

Anti-Rh antibodies are of the IgG class and easily cross the placenta. If the mother 

becomes pregnant again and the baby is Rh-positive, Mom's body will attack the 

erythrocytes of the fetus causing anemia. As a result new blood cells are made 

(erythropoiesis) and released as immature nucleated cells (erythroblasts). Bilirubin, 

the byproduct of hemoglobin breakdown, is transported across the placental carrier 

into the maternal circulation and is excreted by the mother. Hyperbilirubinemia 

occurs in the neonate after birth because excretion of lipid-soluble unconjugated 

bilirubin through the placenta no longer is possible.

Fetuses that do not survive anemia in utero usually are stillborn exhibiting hydros 

fetalis.

hyperbilirubinemia

Occurs in the neonate after birth because excretion of lipid-soluble unconjugated 

bilirubin through the placenta no longer is possible.

ABO incompatibility

Hemolytic disease that occurs when the mother's blood type is O and the newborn's 

is A, B, or AB. Usually so mild that it does not require treatment and may resolve 

spontaneously after birth without life-threatening complications.

RhoGAM

Used to prevent an immune response to Rh positive blood in mothers with an Rh 

negative blood type. Given with 72 hours of exposure to Rh-positive erythrocytes 

(essentially at birth). Given after each and every Rh-positive baby as well as 

miscarriages. It is also given at 28 weeks gestation to Rh-negative mothers with 

Rh-positive partners.