non syndromic inheritable teeth abnormalities

ความผิดปกติของฟันแบบพันธุกรรมไม่เข้ากลุ่มอาการ non syndromic inheritable teeth abnormalities

1. Dentinogenesis imperfecta (DI)

ถ่ายทอดแบบ AD

ชุดฟันที่เป็นปัญหา ทั้งฟันน้ำนมและฟันแท้

ลักษณะฟัน เทา เหลือง น้ำตาล ตัวฟันกว้าง คอแคบ เหมือนดอกทิวลิป อีนาเมล เปราะ แตกง่าย เหลือแต่เนื้อฟัน (Dentin)

ลักษณะรังสี ฟันเป็นของแข็งทึบ ไม่มีโพรง ไม่มีช่องรากฟัน

ลักษณะอื่นที่พบ บางรายมีหูหนวก (DFNA39 mutation ร่วมด้วย)

ตำแหน่งยีน โครโมโซม คู่ที่ 4 4q21.3 ยีน code dentin sialophosphoprotein (DSPP) ซึ่งเป็นโปรตีนที่เป็นองค์ประกอบสำคัญมากกว่า 50 % ในเนื้อฟัน ในส่วนที่ไม่ใช่คอลลาเจน A15V, P17T, V18F, Q45X

Differential diagnosis กับ osteogenesis imperfecta แต่โรคนี้มีแต่ผิดปกติที่ฟัน

การจำแนกชนิด
1. DI type I with OI (Osteogenesis imperfecta)
2. DI type II without OI
3. DI type III พบน้อยมาก และลักษณะกลับกันคือ เนื้อฟันมากไปเหมือนเปลือกหอย แต่ก็พบการกลายพันธุ์บนยีนที่ตำแหน่งเดียวกันกับ type II (allelic variant)







2. Dentin Dysplasia type I and II (DD I and DD II)

Type I ชื่ออื่น Rootless teeth, Radicular Dentin Dysplasia

ถ่ายทอดแบบ AD, มีรายงาน AR homozygous mutation ของยีน NFIC

ตำแหน่งยีน ยังไม่ทราบ

ลักษณะฟัน ภายนอก จะมีสีและรูปร่างค่อนข้างปกติ อาจจะสีเงาๆ ออกฟ้า หรือ น้ำตาลเล็กน้อยได้บ้าง
อาจเป็นฝีได้

ลักษณะ systemic มีรายงานพบลักษณะฟันแบบนี้ในคนไข้ที่มีลักษณะของ EDS type III (hypermobility syndrome ได้) มีรายงาน sclerotic ของ long bone ได้

ลักษณะทางรังสี ไม่มีรากฟันเลยและ มีรอยดำรอบๆ apical area หรือมีรากสั้นๆ ไปจนกระทั่งมีรากยาวปกติ แต่โพรงฟันแคบมาก และอาจมีหินปูนในโพรงฟัน (pulp)
















Type II OMIM #125420 (Gene DSPP 125485)
ชื่ออื่น
DTDP2DENTIN DYSPLASIA, SHIELDS TYPE IICORONAL DENTIN DYSPLASIAANOMALOUS DYSPLASIA OF DENTINPULPAL DYSPLASIAPULP STONES

ถ่ายทอดแบบ AD น่าจะเป็น allelic variant ของ DI-II พบในตระกูลเดียวกันได้

ตำแหน่งยีน 4q21.3 DSPP gene Y6D (Rajpar et. al 2002)

ลักษณะฟัน ฟันน้ำนมจะมีสีเหลือง โปร่งแสง และไม่มีโพรงฟันเลย ส่วนฟันแท้จะมีสีภายนอกปกติ รากปกติ แต่โพรงฟันขึ้นไปถึง ตัวฟันด้านบน บานออกคล้ายเปลวไฟ หรือ thistle tube

Gene patenting: Pros and Cons

Pros

Centralization, specialization

Rewarding, Incentives for further inventions

No further secrets

Cons

Quality control

Accessibility

Cost

Lost of expertise

Right of previous contributed researchers

I have found this below interesting essay about gene patenting wrote by an anonymous author in the internet.

1
I. Patents for Biotechnology
（Pros and cons of genetic patents）
Biotechnology is closely related to drug industries. 90% of biotechnology sales in the
U.S. are from pharmaceuticals. The number of granted biopharmaceutical patents in the
U.S. is 5170 in 2001, while only 533 in Europe.1 This result depends on the difference
between them about genetic patents policy.
There are significant advantages for allowing genetic patents. First, the patents in this field
clearly promote invention. The drug industry is the field where patent protection is easier to
enforce because of the relative simplicity of the industry and its products. Second, the
patents encourage many entities get into the research. Until the 1970s, nearly all molecular
biology research was government or university sponsored. After genetic patents were
admitted in the U.S., small firms can raise funds for research activities by making their
knowledge into assets through patent system. New drugs require knowledge from broad
fields, so the collaboration among many entities is effective for making good research.
Third, the patents have an effect to promote diffusion of new research by filing research
1 Derwent Intellectual Property. Patenting in the biopharmaceutical industry- comparing
the US with Europe. December 2002.
2
contents.
On the other hand, disadvantages of allowing genetic patents are as follows. First, too
many patents may adversely slow down research activities. As the risks to infringe existing
patents grow, pharmaceutical industries are forced to specialize in particular fields.
Increased costs for litigation concerning patents might also impede research activities.
Second are the adverse effects on the diffusion of the products. Allowing genetic patents
will lead the price of drugs increase due to the license fees. This price increase can diminish
high social rates of return of the drugs by restraining their spreading to the public.
Furthermore, patent holders might ask the withdrawal of drugs that infringe their patent
rights, even if the drugs are already widely used.
(Recommendation)
I recommend that EU should make genetic patents easier as the U.S. already did by
following reasons. First, the needs for genetic patents from creators are very high. The
number of biopharmaceutical patent applications has been increasing continuously. It has
become from 430 in 1992 to 3544 in 2001.2 It means that creators regard genetic patents as
2 In the U.S., the number of application in this field is 34,527 in 2001. Ibid.
3
useful to advance their innovative activities.
Second, relaxation of the conditions of genetic patents is essential to promote the
international competitiveness of Europe in biotechnology. Industries in this field have
broadened their activities worldwide (We must note that leading companies in the U.S. and
Japan has already applied and held biopharmaceutical patents in Europe.). Collaboration
among many entities including government, universities and industries is important in
biotechnology to accumulate knowledge from various fields. Genetic patents will promote
the growth of firms and universities addressing the challenging research in Europe.
How do we deal with the disadvantages expected? The problem of patent thickets might
occur, but it can be solved by the vertical integration and cross licensing among patent
holders. As for the litigation, some special measures to restrict the increase of the costs (e.g.
compulsory arbitration) are the possible solution.
The problem of diffusion is more serious. I think this problem should be solved by the
support from the government. It takes enormous costs to make innovations or inventions in
biotechnology. The costs should be shared properly between creators, consumers and the
government. The subsidies from the government will contribute to restrain the price
increase due to the license fees. Furthermore, compulsory licensing system will prevent
4
creators from keeping their patented knowledge unused.
By introducing these methods, European biotechnology firms can increase their
incentives for innovative activities, which will strengthen their competitiveness in the
world. The welfare of European citizens will be also promoted by the development of new
drugs and treatments using innovative biotechnology. We must note that effective measures
to secure the appropriate diffusion, namely, the speedy distribution of the products with
reasonable price, should be implemented at the same time by governmental assistance.
Overall, this is a strong answer. The author clearly states both the pros and cons of
patent protection for biotechnology. Note how each point is clearly emphasized (e.g.
“first”, “second”, “third”) making it easy for the reader to follow the argument.
Similarly, in making policy recommendations, the author again clearly states the reasons
why the recommendation is made. Also, the author does a good job of noting the
potential problem of diffusion, and creatively offers a potential solution.
One caveat: the answer could be strengthened with a stronger introduction. Although
each section is well-written, it would help to have a statement of the final
recommendation at the beginning of the answer, so the reader can evaluate the pros and
cons of patenting with the final recommendation in mind.

Personalized medicine conference

Go to this link:http://www.hpcgg.org/PM/2007/index.jsp
Personalized medicine : A conference held by Harvard Medical School November 29-30 2007

How Did DNA Testing Children Begin?

The story behind the first maternity and used for legal purposes.
This year marks the 20th anniversary of a remarkable discovery which forever changed the legal profession. In 1985, Alec Jeffreys (now Sir Alec), a young genetics professor at Leicester University, discovered DNA fingerprinting--the technique which allows for unambiguous human identification as well as relationship identification between different people. Since then, has emerged as a powerful tool in both civil and criminal justice systems. DNA testing can not only reveal whether two or more individuals are related but can also determine the nature of this relationship. Today, it is possible to identify people by a single hair, as well as obtain information about their gender, ethnic background, and nearly their exact age.


In non-criminal legal practice, DNA testing is used primarily for immigration and child support cases. In 2004, more than 7,000 DNA tests were conducted in the UK for these purposes. When no reliable documentary evidence is available, DNA testing can assist in determining varying degrees of relatedness between individuals, as well as their ethnic background.
The landmark immigration case Sarbah vs. Home Office (1985) was the first to use DNA testing to prove a mother-son relationship between Christiana Sarbah and her son Andrew.
The case started in 1983 when Andrew, then 13, arrived in England after a long stay in Ghana with Christiana's estranged husband. Immigration officials held him at Heathrow Airport, claiming his passport was forged, or that a substitution had been made. Only after intervention by a local MP was Andrew allowed to stay at his family's home in London.



Various genetic-determining tests showed that Christiana and Andrew were almost certainly related; however, it was impossible to determine whether Christiana was his mother or merely an aunt (Christiana has several sisters in Ghana). The photographic evidence and depositions were rejected at an immigration hearing, but deportation was delayed pending an appeal.
Around the same time, an article in The Guardian reported the discovery of DNA fingerprinting by Prof. Alec Jeffreys and his team at the University of Leicester. After reading about their work, the legal team dealing with the case approached Prof. Jeffreys, and he agreed to take on the case. In order to prove that Christiana was Andrew's mother, a DNA test was performed on blood samples from Christiana, Andrew, an unrelated individual, and Christiana's three undisputed children: David, Joyce, and Diana.



Using a recently discovered DNA probe, a DNA fingerprint was produced which confirmed that Christiana was indeed Andrew's biological mother, and that David, Joyce and Diana were his siblings. Based on this evidence, the case was dropped by the Home Office and massive press coverage ensued. The discovery of DNA fingerprinting had huge implication for the non-criminal legal system and led to an overhaul of the UK's Immigration legislation. Current UK immigration legislation accepts results of DNA testing as the ultimate proof or relationship between a child and his or her relatives. Accordingly, DNA test results will normally (although not invariably) provide conclusive evidence as to whether a child is related, as claimed, to one or both of his alleged parents.



Before January 1991, it was up to the applicant to decide whether or not to obtain DNA evidence in support of his or her application or appeal. In January 1991, a government scheme was introduced, which enables entry clearance officers (ECO) to offer to arrange DNA tests in cases where they are not satisfied that persons seeking admission as children are related to their UK sponsor.

genetic engineering (11) DNA preparation for cloning

DNA preparation for cloning from mRNA
1.see for abundance of mRNA -partial answer about function
eg> young RBC - large amount of Hemoglobin mRNA, chicken fallopian tube - ovalbumin mRNA 100000 molecule/cell( in contrast others species (12507) toally less than 100000
2.do not need post transcriptional modification machine of eukaryotes

Method
1. mRNA--> reverse transcriptase --> cDNA (complementary DNA)

Primers: oligo dT --> digest RNA with alkaline
sscDNA have a hook use as primer for DNA polymerase --> ds cDNA with hair pin end
S1 nuclease--> two blunt end

primer for this second strand is not so effective and S1 nuclease can shorten or unequal cut

2. use RNAse h replace alkaline --> random digest so RNA can be use as primer
second strand production by DNA polymerase I--> T4 DNA polymerase cut to be blunt end

DNA preparation by chemical synthesis
up to 50 nt
oligonucleotides and link with DNA ligase
eg: interferon gene : 66 oligonucleotides to 514 bp
commonly use for probe, primer, linker synthesis

Method
1. Phosphate triester
add protective group at amino group of A, C (benzoyl), G (isobutyryl)
add protective roup at 5' with dimethoxytrityl chloride (CH3O)2Tr-
add p-chlorophenylphosphorodichloride at 3' to link with another nucleotide [with 3' protected (berta cyanoethanol) and dimethoxytrityl at 5' removal with benzebnesulfonic]
react with triisopropylbenzenesulfonyl chloride
--> all protected dinuleotide--> select removal to control direction of synthesis

can be automated when attached with solid phase
10-20 nt in 2-3 days
2. Phosphite triester
linker is nucleoside 3- phosphoramidite
different protected group and removers
15 min 50 bp good quality