Sickle Cell Anemia Presence in Africa

    The inspiration of this article comes from a conversation I had today with a co-worker whose ancestry descends from Nigeria. We work in an emergency room together, our experiences today is what initiated this conversation. Sickle Cell Anemia (SCA) is a homozygous recessive trait that causes an abnormality amongst red blood cells, hemoglobin is the protein in your red blood cells that is responsible for carrying oxygen. Sickle cell anemia is common in places where malaria amongst mosquitoes is prominent, natural selection promotes family pedigree who are resistant to the malaria disease. In turn, if a person is immune malaria they unfortunately carry the sickle cell trait. This immune population can either be heterozygous or homozygous recessive. Being diagnosed with sickle cell anemia brings many potential health risks including sickle cell crisis, vaso-occlusion blood clots to digits in infants, the spleen, lungs, etc. If someone has sickle cell anemia, they are immune-compromised, if their body were to come in contact with common bacterias that cause pneumonia, or common colds, without proper medical attention these bacterias can yield fatal results. The first link of my article is a video that gives insight on the pathophysiology, potential health risks, and treatment methods of sickle cell anemia. I recommend giving it a watch, as it is quite fascinating. 

    Reflecting back on the conversation with my co-worker, she began to explain some methods countries in Africa and South-East Asia use to try to mitigate the presence of this brutal disease in their countries. In her home country, it has gotten to the point where churches will not conduct a marriage unless the genotype of the parents is confirmed. If the engaged couple runs the risk of producing offspring who can suffer from SCA, the church will not conduct the marriage. While some may regard this as unethical, the prevalence of sickle cell in their country is alarming. It is estimated about 150,000 children in Nigeria have SCA, and nearly 25% of the country are heterozygous carriers of the trait. Since there is no cure for the disease, the only way to lower these numbers is to try to prevent it from being passed on. This was a very interesting topic to me, if anyone has more insight on this please leave a comment as I would like to learn more. 

Link: https://www.youtube.com/watch?v=fIIJmg_1hv0

Link: https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-019-0376-8

Link: https://www.cdc.gov/ncbddd/sicklecell/data.html 

Genetic Risks of Inbreeding

    In our society today the term "inbreeding" is typically only used when it pertains to animals. For example, a dog having blue eyes is a recessive trait to the dominant brown eyes. The most efficient way to reproduce a generation of dog offspring with blue eyes is breed a male and female dog that carry the blue eyed phenotype, meaning they are homozygous recessive for it. As illustrated in the flow chart, it is possible for an offspring to inherit the homozygous recessive trait from parents who do not physically show it. These are the risks that are posed when inbreeding occurs amongst humans. Hypothetically, imagine the recessive trait in this instance was a chronic auto-immune disease, skeletal abnormality, or chronic genetic disorder. According to a study done in 2011, inbreeding practically doubles a person's susceptibility to inheriting a genetic disorder. If a person were to mate with someone outside of their family gene pool, if they do not carry the recessive trait for the unfavorable disease the offspring can resist being born with that phenotype. 

    There are many undesirable traits that put an offspring at risk when inbreeding. The offspring is susceptible to reduced fertility, birth rate, and immune function. They also have increased risk of cardiovascular disease, facial asymmetry, and risk of genetic disorders. The rates of child mortality is higher, and the growth of the human body as an adult is smaller. The most common genetic disorders that inbreed offspring face are schizophrenia, limb malformation, blindness, congenital heart disease, and neonatal diabetes. 

Link: https://www.thoughtco.com/inbreeding-definition-effects-4171861

Link: https://www.bbcearth.com/news/what-are-the-effects-of-inbreeding

One Family's Struggle With Microcephaly

In 2006, Christine Grounds gave birth to a child with microcephaly, the birth defect caused by the Zika virus that causes malformed heads and stunted brain development in children. The doctors were not entirely sure what this meant for the newborn, Nicholas Mir. This was much before the Zika outbreak that occurred this year that had spread from Brazil. Since the outbreak, the CDC estimates that there are over 2,600 pregnant women who have tested positive for Zika in the US and its territories, along with thousands more around the world. All these women may potentially give birth to children with microcephaly. The severity of microcephaly varies greatly, but one of the most difficult parts of this disorder is that is very difficult to identify until late in the pregnancy, leaving thousands of women with the agonizing choice of waiting anxiously and hoping for the best or abortion. Mrs. Grounds offered to share her experience raising Nicholas when the outbreak occurred. She describes how difficult it was in the beginning, but that Nick progressed quickly once he reached age eight. However, unlike many, Nicholas is fortunate to be able to attend an excellent private school on the Upper West Side that provides great care and has helped him get to where he is today.

Dr. Wendy K. Chung is a director of the clinical genetics program at Columbia University Medical School and she met Nicholas for testing when he was a baby, as his parents were hoping to find answers in his genetic makeup. At first, the tests were not successful because there were not enough facts and developed science, but about three years ago, Dr. Chung finally had an answer. Nicholas was autosomal recessive for the microcephaly gene, meaning both of his parents carried the recessive gene for the disorder. They had a second child before these results were discovered, assuming that it was highly unlikely for their second child to have microcephaly as well, but as it turns out, the odds were one in four.
I thought it was incredibly helpful that Christine Grounds chose to share her story about Nicholas to help others dealing with microcephaly or facing the possibility of having a child being born with microcephaly. Because is an autosomal recessive disease, pregnant parents with the Zika virus can have the genome of the father mapped out in order to see if he carries the recessive gene to further evaluate the odds of having an affected child.

Neimann Pick Type C-1 Treatment

Parents Hugging Daughters with Neihmann Pick Disease

The Neimann Pick Type C-1 disease is a lethal and inherited disease against the body's metabolism for lipids and cholesterol. There is a new treatment that come out of the National Institutes of Health. There was a long detailed report of using model organisms of mice and then cars and it showed that the drug made of cyclodexetrins can slow the disease, prolong life, and minimize some of the symptoms of the condition. Now there is a competition between which company will be able to make human trials successful from Vtesse to the NIH and CTD Holdings.

"In mouse models of the disease, cyclodextrin administered peripherally delayed disease onset, reduced brain accumulation of fat, and lengthened life significantly, several published studies have found. In presentations this summer, CTD representatives reported anecdotal cases of neurological improvements- such as motor skills and speech- in children treated intravenously with the company's cyclodextrin on a compassionate use basis, including the Hempels' daughters. The company further notes that the IV delivery method may protect other organs affected by NPC."

The reasons why this disease is related to our class are based on two idea. The idea of using a model organism first is along the ethical ideas of genetics practice and medicinal practice of using a non-human organism first to model the possible human reactions and interactions. Along with this idea comes the idea of inheritance through families and all of the forms of Niemann Pick are autosomal recessive inheritance based.

"This means that both parents are carriers each carry 1 copy of the abnormal gene without having any signs of the disease themselves. When both parents are carriers, there is a 25% chance that their child will have the disease and a 50% chance that their child will be a carrier."

I think it is wonderful how medicinal competition and betterment of medicine and technology is pushing for a treatment for this inherited disease, but I am also wondering if there are any pre-zygotic treatments for conception that could prevent a child from being born with this disease. i have always been interested in genetic disease prevention and hopefully technology of current treatment will eventually develop to the pre-conception stage of the disease.

Genetics Could Be Causing Intellectual Disabilities

In recent studies, Dr. John Vincent has been researching the genetic causes behind intellectual disabilities.  According to this article although there may be other causes behind intellectual disabilities in children such as trauma in the womb, but genes are one of the main sources. Dr. Vincent performed these studies on families where the popular culture includes intermarriage between first cousins.  Such inbreeding could produce a larger likely hood that the children of these couples will receive defective recessive genes.  Although this decreased cognitive development is extremely common within inbreeding families, it is also found in non inbreeding situations.  This and other research has shed light on just how many genes can and do affect the inheritance of intellectual disabilities.  This supporting article discusses a study that researches the affects METTL23 gene has on cognitive development.

I think that this research will be very beneficial for scientists in the field of cognitive studies.  Research has been done to prove just how much traumatic injuries can affect brain development and functioning but more research needs to be performed to see just how genes affect the brain.  The research could open many more doors for scientists to genetically test parents prior to having children.  Since the brain development is such a vital part of growing up it is important to be aware of possible troubles. Genetic testing can help parents know the risk of their child inheriting such detrimental genes.  I am in full support of parents being pre-tested before having children in order to understand the risk of having a child.  

Descendants of the Blue Skinned Fugates

Recently, it was found in medical records that a patient was born in Kentucky in 1975 with a condition called Methimoglobinemia. This blood disease was popularized by the account, "The Blue People of Troublesome Creek".  The work outlined the Blue Fugates, the descendants of a French immigrant that settled in Kentucky in the early 1800s. Many members of the family line had this condition, and were noticeably blue. The condition causes the skin to turn blue, and is extremely rare. Over the past century, it has rarely been seen anywhere but Kentucky, in a small geographical region. It has nothing to do with the environment there, but with genetics.

[caption id="" align="alignnone" width="446" caption="The Fugate Family"][/caption]

Methimoglobinemia is a recessive condition that is mostly perpetuated by inbreeding, which is exactly what was going on in the Fugate family line. The information found in medical records from 1975 was that of Benjamin Stacy, who has been proven to be a direct bloodline to the infamous 19th century family.