Sickle cell disease
Sickle cell disease is an inherited blood disorder that affects red blood cells. People with sickle cell disease have red blood cells that contain mostly hemoglobin* S, an abnormal type of hemoglobin. Sometimes these red blood cells become sickle-shaped (crescent shaped) and have difficulty passing through small blood vessels.

When sickle-shaped cells block small blood vessels, less blood can reach that part of the body. Tissue that does not receive a normal blood flow eventually becomes damaged. This is what causes the complications of sickle cell disease. There is currently no universal cure for sickle cell disease.

The origin of the mutation that led to the sickle cell gene was initially thought to be in the Arabian peninsula, spreading to Asia and Africa. It is now known, from evaluation of chromosome structures, that there have been at least four independent mutational events, three in Africa and a fourth in either Saudi Arabia or central India.[3] These independent events occurred between 3,000 and 6,000 generations ago, approximately 70,000-150,000 years.

Malaria
The plasmodium parasite that causes malaria is transmitted from mosquitos to men. The parasites spend part of their life cycle in the mosquito and part of it in the human host. The infective plasmodial sporozoites enter the bloodstream from the saliva of the feeding female anopheles mosquito. The Kupfer cells of the liver clear the sporozoites from the blood stream and kill many of the organisms. A fraction of the sporozoites escape destruction however, and penetrate the hepatocytes where they take up residence.

The parasites within the hepatocytes transform into a new entity called schizonts. The nuclear genetic material in the schizonts replicates to the point that the hepatocytes are totally filled with new forms called merozoites. A single schizont can produce thousands of merozoites. Erumpent hepatocytes release the merozoites into the bloodstream where they invade circulating red cells. After penetrating the red cells the merozoites assume a ring form called trophozoites. These organisms consume hemoglobin in erythrocytes and enlarge until they fill the cell completely. During their growth, the trophozoites metamorph into schizonts and produce new merozoites inside the red cells. The red cells subsequently lyse and release merozoites that can penetrate new red cells and restart the pernicious process.

Some of the trophozoites in the red cells take a different developmental pathway and form gametocytes. Gametocytes are the sexual form of the parasite and do no lyse the red cells. A mosquito taking a blood meal from a person whose red cells contain gametocytes acquires the malarial parasite. The sexual reproduction cycyle then  begins in the mosquito. The mosquito subsequently transmits the parasite when it attacks another human host.

Malaria Defense
The complex nature of the malaria parasite life cycle in the human host presents several points at which the organism could be targeted for destruction. The sporozoites injected into the blood stream with the initial mosquito bite are attacked there by components of the immune system. These include antibodies, lymphocytes called "natural killer cells" as well as lymphocytes that attack the malarial parasites because of prior exposure to the organisms (conditioned lymphocytes).
Host immunity is crucial to survival of people infected with the malaria parasite. This is particularly true with respect to the nocuous falciparum parasite. The immune system works best when it has been primed against the invader. Children who suffer their first or second bout of malaria have not developed the immune response needed to provide adequate defense against the parasite. This explains in part the high mortality seen in children infected with P. falciparum. Vaccines are a common way of achieving host immunity prior to pathogen exposure. Polio immunization is a well-known example. Unfortunately, the malarial parasite constantly changes its immune makeup, thereby frustrating efforts to produce an effective vaccine.

The intrahepatic phase of malarial parasite growth presents another potential point at which to attack the organism. No mutation in the structure or function of hepatic cells that kills the malarial parasite or retards its growth is known.

The last point at which life cycle of the malarial parasite can be frustrated in humans is at the phase of red cell invasion and multiplication. Red cells are constantly created and destroyed as part of their life cycle. A mutation that somehow destroys both the infected red cells and the parasite could therefore eliminate the malaria parasite.  The destroyed infected cells would be replaced by new, healthy cells.

Sickle hemoglobin provides the best example of a change in the hemoglobin molecule that impairs malaria growth and development. The initial hints of a relationship between the two came with the realization that the geographical distribution of the gene for hemoglobin S and the distribution of malaria in Africa virtually overlap. A further hint came with the observation that peoples indigenous to the highland regions of the continent did not display the high expression of the sickle hemoglobin gene like their lowland neighbors in the malaria belts. Malaria does not occur in the cooler, drier climates of the highlands in the tropical and subtropical regions of the world. Neither does the gene for sickle hemoglobin.

Sickle trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic. Sickle cell trait provides neither absolute protection nor invulnerability to the disease. Rather, people (and particularly children) infected with P. falciparum are more likely to survive the acute illness if they have sickle cell trait. When these people with sickle cell trait procreate, both the gene for normal hemoglobin and that for sickle hemoglobin are transmitted into the next generation.

[pranala luar disembunyikan, sila masuk atau daftar.]
[pranala luar disembunyikan, sila masuk atau daftar.]
[pranala luar disembunyikan, sila masuk atau daftar.]

Baru nemu & baca bbrp artikel yg menarik. Baru tau skarang kl ternyata sickle cell disease menyebabkan resistansi thd malaria...
Jadi ini berkah atau musibah ya? 
Atau salah satu bentuk evolusi manusia?  ???

KutipAtau salah satu bentuk evolusi manusia? 

Kalau ini termasuk evolusi, sudah pernah dengar lama. Tapi lebih ngertinya baru kemarin malam, hasil ngobrol2 dengan bung reborn 

Di link jesuisnoel yg terakhir itu disebutkan gini:

A common misconception is that natural selection somehow produces a desirable change: "giraffes grew long necks in order to reach leaves high in trees." This is not the way in which natural selection works, however. Natural selection does not promote or produce a change in an organism. Rather, a change occurs because of spontaneous alterations or mutations in the DNA genetic code. Changes in the genetic code can alter the physical characteristics of the organism. If the new trait gives the organism a survival or reproductive advantage over its fellows, the new trait will be represented in the second generation more frequently than it was in the first generation. This is the natural process by which  advantageous characteristics are selected.


Jadi, emang evolusi. Tapi, saya jadi penasaran, konsep evolusi dan seleksi alam menurut jesuisnoel bagaimana? 


_{*lagi semangat diskusi, gara2 reborn} 

Kutip dari: peregrin pada Desember 05, 2007, 02:31:10 AMKalau ini termasuk evolusi, sudah pernah dengar lama. Tapi lebih ngertinya baru kemarin malam, hasil ngobrol2 dengan bung reborn 

wah... fitnah ini  siapa yang mulai pembahasan ttg aging duluan 
Justru gw yg dengerin penjelasannya 

Kutip dari: peregrin pada Desember 05, 2007, 02:31:10 AM
Natural selection does not promote or produce a change in an organism. Rather, a change occurs because of spontaneous alterations or mutations in the DNA genetic code. Changes in the genetic code can alter the physical characteristics of the organism.

di sini letak misconception-nya yahh... wuih, thanks dah dikasihtau ya jesuisnoel dan peregrin.
rada ngerti deh sekarang.

KutipJadi, emang evolusi. Tapi, saya jadi penasaran, konsep evolusi dan seleksi alam menurut jesuisnoel bagaimana?   

Evolusi itu...hereditary gradual genetic change...*hehe, definisi sendiri..salah ga? *

Dulu kan diajarin di sekolah evolusi merupakan bentuk adaptasi thd seleksi alam yah...dari sini dikasihtau kalo evolusi terjadi, dan alam menyeleksi mahluk2 hasil evolusi yang unggul.

Nanya dong kak..
Jadi evolusi/mutasi/alterasi genetik itu terjadi scr random ya...? Kalo evolusi dianggap 'advantage', dalam kasus ini bukannya lebih banyak efek negatifnya (makanya considered as disease)? E.g.: penderita sickle cell harus tranfusi tiap bulan krn hemoglobinnya berumur lebih pendek drpd yang normal. Consequently, bisa terjadi penimbunan besi di organ2 tubuh...dan akhirnya komplikasi juga.

Kutip dari: jesuisnoel pada Desember 21, 2007, 06:21:26 PM
Jadi evolusi/mutasi/alterasi genetik itu terjadi scr random ya...? Kalo evolusi dianggap 'advantage', dalam kasus ini bukannya lebih banyak efek negatifnya (makanya considered as disease)?

kak jesuisnoel  ...

kalo ga salah waktu ngobrol dulu, reborn pakai istilah: "kebetulan tidak beruntung"  untuk menggambarkan mereka2 yg tidak survive - disebut kebetulan krn mutasi genetik terjadi scr random.

Di daerah endemic malaria, mutasi sickle hemoglobin tsb memang advantage toh.
Alam sepertinya memang bekerja dg cara trade-off. Jadi proses evolusi bukan memberikan solusi final yang akan menghasilkan organisme yang selalu lebih "baik/sempurna/sehat". Proses evolusi = proses kompromi, untuk situasi tertentu. Hasil kompromi ini yang diturunkan (karena survive, terseleksi oleh alam, pada saat itu).

Contoh lain: heterozigot gene yang memberi keuntungan survival terhadap demam tifus, diduga juga bertanggung jawab terhadap timbulnya penyakit cystic fibrosis.


Aku attach ya satu artikel lama yang menarik, judulnya "Evolution and the Origins of Disease".
Isinya antara lain tentang berbagai macam kontradiksi yang terjadi di tubuh kita, akibat adanya trade-offs, constraints, defense mechanism, conflicts of interest, dsb. Juga sedikit tentang konsep Darwinian medicine.

Kutipan dari artikel tersebut:

KutipThe assumption that natural selection maximizes health is incorrectâ€"selection maximizes the reproductive success of genes. Those genes that make bodies having superior reproductive success will become more common, even if they compromise the individual’s health in the end.

ternyata jika kita pelajari mendalam,kebesaran Tuhan YME sangat besar, menjadikan diri ini amat berdosa karena kita slalu melupakan nikmat Allah swt yang telah diberikan kepada kita yang tidak dapat kita hitung.........

Kutip dari: peregrin pada Januari 24, 2008, 06:43:27 AM
kak jesuisnoel  ...

Thanks ya bu guru...eh, kak peregrin  .
Artikelnya lucu . Jadi makin interest thd Darwinian Medicine nih...padahal lagi baca 1 bukunya aja blm selesai2 (kayanya udah diringkasin di artikel itu deh, heheh *dasar males*) :p

waktu aku ikut pelatihan OSN biologi,diterangkan kalo orang Afrika yang kena sickle cell gak bakal kena anemia...mungkin plasmodiumnya malah gak bisa berkembang dalam bentuk sel darah merah yang gak normal kali yaa?Tuhan adil juga kan,orang Afrika banyak yang mati gara-gara malaria tapi yang sickle cell hidup..kendati penyakit kelainan genetis ini lumayan parah juga...

PS:eh,kacau banget sih pada bilang kalo penyakit sickle cell ini mekanisme evolusi alam dan evolusi..penyakit ini ada bukannya adanya kromosom gagal berpisah waktu meiosis sel gamet??ya gak harus meiosis juga sih,secara kalo waktu kita pada tahap blastula-gastrula,sel yang bakal jadi sel darah merah mengalami mitosis, ada kromosom yang gagal berpisah makanya terjadilah itu penyakit

Kutip dari: lovianettesherry_gonz pada Juli 09, 2008, 07:14:40 PM
PS:eh,kacau banget sih pada bilang kalo penyakit sickle cell ini mekanisme evolusi alam dan evolusi..penyakit ini ada bukannya adanya kromosom gagal berpisah waktu meiosis sel gamet??ya gak harus meiosis juga sih,secara kalo waktu kita pada tahap blastula-gastrula,sel yang bakal jadi sel darah merah mengalami mitosis, ada kromosom yang gagal berpisah makanya terjadilah itu penyakit

Nah, gmn ini bisa terjadi? Kenapa bisa mutasi seperti ini? Mutasi gen ini terjadi secara acak.
Di artikel yg di attachment itu dijelasin ttg trade-off.  Coba baca deh artikel yang dikasih jesuisnoel, [pranala luar disembunyikan, sila masuk atau daftar.],  n attachmentnya peregrin. Di situ diterangin misalnya ttg prinsip Darwinian Medicine.