CC BY
18
Вестник Ка^НЖУ №1-2018
У. Диакбарова1, Ш. Шамилулы2, Р. Джумашева1
1СЖ.Асфендияров атындагы К,азац ¥лттыц медицина университету Молекулалыц биология жэне медициналыцгенетика кафедрасы 2Сулеймен Демирел университетi, Алматы, Казахстан, Компьютерлк гылым кафедрасы
ГИСТОН БИОСИНТЕЗ1 КЕЗШДЕМАЦЫЗДЫKЫЗМЕТАТKАРАТЫНSLBPАKУЫЗЫ
ty^h: ДНЦ репликация кезшде жасуша гистондар децгешнде жэне ДНЦ синтезiнiц арасында тепе-тецджке ;ол жеткiзiлуiн жэнеS фазасында гистонды белоктар синтезделуiн ;амтамасыз eTyi ;ажет^ фазасында гистонды белоктар биосинтезiнiц шектеулi болуы геномныц тура;тыльиын ;амтамасыз етуде жэне геннщ дурыс регуляциясында мацызды болып табылады.Гистонды белоктар экспрессиясыныц реттелуше, сондай-а; гистондар генiнiц транскрипциясына, аРНЦ тYзiлуге дейiнгi тиiмдiлiгiне, мРНЦ жартылай ыдырау децгейiне жэне арты; тYзiлген гистонды белоктар дегредациясына, гистондар биосинтезшщ ;осал;ы факторы болып табылатын, гистонды; мРНЦ 3'-ушыменStem-Loop Binding Protein (SLBP) акуызымен байланыс жасауынакептеген тарнскрипциялы; жэне посттранскрипциялы; факторлар эсер етедi.SLBP акуызыэкспрессиясы жасушалы; циклдщмРНЦ децгейiнiц аса мацызды емес eзгеруiмен реттеледiжэне осы реттелу S фазасы кезiнде гистондардыц кеп мелшерде тYзiлуiн ;амтамасыз етедi.SLBPак;уызы децгеш S фазасы кезiнде ете жогары жэне M бен G1 фазасында темен болады. Ма;алада керсетiлетiн керсеткштер S фазасы SLBP акуызыныц шектеулi экспрессиясыныц децгейi гистонды; мРНЦ биосинтезi Yшiн мацызды екендiгi керсетедi.
TY^H4i свздер: байланыстырушы белок(SLBP), гистонды мРНК, жасушалы; цикл, акуыздыц бузылуы, mRNA гистоныныц емi.
У. Диакбарова1, Ш. Шамилулы2, Р. Джумашева1
1Казахский Национальный медицинский университет имени С.Д.Асфендиярова Кафедра молекулярной биологии и медицинской генетики 2Университет Сулеймана Демиреля, Алматы, Казахстан Кафедра компьютерных наук
ЖИЗНЕННЫЙ ЦИКЛ SLBP ОСНОВНОГО БЕЛКА В БИОСИНТЕЗЕ ГИСТОНА
Резюме: Во время репликации ДНК клетки должны достичь очень тонкого баланса между синтезом ДНК и уровнями гистонов, обеспечить синтез гистоновых белков только фазы S. Ограничение биосинтеза гистонов на S-фазы имеет решающее значение для поддержания геномной стабильности и правильной регуляции генов. Многие транскрипционные и посттранскрипционные факторы вносят вклад в регулирование экспрессии белков гистонов, включая транскрипцию генов гистонов, эффективность обработки до мРНК (процент зрелой мРНК, который достигает цитоплазмы), изменение периода полувыведения мРНК и деградация избыточных гистоновых белков. Stem-Loop Binding Protein (SLBP), связывается с З'-концами гистоновых мРНК и является ключевым фактором биосинтеза гистонов. Экспрессия SLBP регулируется клеточным циклом без значительного изменения уровня его мРНК, и эта регуляция отвечает за возникновение объемного производства гистонов во время фазы S. Уровень SLBP является высоким во время фазы S и ниже в фазе M и G1 до следующей фазы S. Было обнаружено, что SLBP деградирует в конце фазы S из-за двойного фосфорилирования, инициированного циклина A / CDK2 и аналогично в G1, стабильность SLBP, по-видимому, низка. Белок SLBP не деградирует в конце S-фазы и влияет на скорость репликации ДНК. Эти данные показывают, что S-фаза, ограниченная экспрессией SLBP, очень важна для биосинтеза гистоновой мРНК. Ключевые слова: связывающий белок (SLBP), гистоновая мРНК, клеточный цикл, деградация белка, обработка мРНК гистонов.
UDC 616-01/09
A. Karaca
Massachusetts General Hospital and Harvard Medical School 55 Fruit Street Boston, MA 02114, Boston, USA
RARE GENETIC DISEASES RELATED TO BRACHYDACTYLY
Brachydactyly (BD) refers to the shortening of the hands, feet or both, and it has a clinical spectrum ranging from minor digital hypoplasia to complete aplasia. The index and small fingers are the most commonly affected digits, and the middle phalanx is the most commonly affected bone. It is inherited in autosomal dominant manner and has reduced penetrance and variable expressivity. The various types of isolated brachydactyly are rare, except for types A3 and D. Brachydactyly can occur either as an isolated malformation or as a part of a complex malformation syndrome. The nature of genetic counseling will depend on the pattern of inheritance of the type of brachydactyly present in the family and on the presence or absence of accompanying symptoms. Thus this review, summarizes the physical and molecular details about different types of brachydactyly and aims to serve as a collective review as a reference to refer. Keywords: Brachydactyly (BD), Genetics; Hand abnormalities; Foot abnormalities; Congenital bone malformations
Brachydactyly is a general term characterized by disproportionately short fingers and toes. It can occur as an isolated finding or as part of a complex syndrome. Many different types of brachydactyly have been identified. Some result in short stature and others are associated with other hand malformations, such as syndactyly, polydactyly, or reduction defects. The index and small fingers are the most commonly affected digits, and the middle phalanx is the most commonly affected bone. Presentation of brachydactyly is highly variable —
a digit may be just slightly shorter because of reduced growth of one phalanx or the metacarpal, or there may be complete absence of one or more phalanges, or there may be complete aplasia of the digit or multiple digits.
The underlying genetic cause of most isolated forms of brachydactyly and many of the syndromic forms has been identified. Many of the isolated forms are inherited in an autosomal dominant manner with variable expressivity and reduced penetrance and in most cases does not present any
Vestnik KaxNMU №1-2018
problems for the person who has it. Treatment depends on the specific type of brachydactyly, but may include plastic surgery, physical therapy and/or ergotherapy.
There are different types of brachydactyly, based on which bones are shortened. This condition can also be a symptom of other genetic disorders. The various types of isolated brachydactyly are rare, except for types A3 and D, which are common, prevalence being around 2% (1) . A search of Online Mendelian Inheritance in Man (4) using brachydactyly as key term provided 232 entries (isolated forms; syndromes with brachydactyly; skeletal dysplasias). A similar search using brachydactyly as search term in the London Medical Databases (LMD) (5) yielded 386 entities. The incidence and prevalence of these entries varied
Table 1 - Classification of Brachydactyly according to Tentamy 2008 (2).
considerably.Brachydactyly can occur either as an isolated malformation or as a part of a complex malformation syndrome. To date, many different forms of brachydactyly have been identified. Some forms also result in short stature. In isolated brachydactyly, subtle changes elsewhere may be present. Brachydactyly may also be accompanied by other hand malformations, such as syndactyly, polydactyly, reduction defects, or symphalangism. One of the most commonly used classifications of brachydactyly based on anatomic grounds was provided by Bell (6) and further elaborated by Temtamy & McKusick (1). The types of branchydactyly is summarized in the table below by Temtamy et al, 2008 (2).
Is ame
S™oir."nis
OMM
Brachydactyly type A
Brachydactyly type Al (EDA1) Farabee type brachydactyly
Brachydactyly type A2 (BDA2) Mchr-Wnedt type brachydactyly
Brachydactyly type A3 (BDA3) Biachymesophalangy Y Br^hydactyly-Clinodactyly
Brachydactyly type A4 (BDA4) Biachymesophalangy II and V Temtamy type brachydactyly
Brachydactyly type AS (BDAi) Absent middle phalanges of digits 2-5 ivitii nail dysplasia
Brachydactyly type B (BDB) Brachydactyly type C (BDC) Brachydactyly type D (KDD) Brachydactyly type E (BDI) Brachymetatarsus TV Sngat'Qiau brachydactyly Kinier deformity
Brachydactyly with hyperphalansisni Ha™ t}pe brachydactyly Stub thumb
Metatarsus IV short Toes: fourth, short
Brachydactyly with major proximal phalangeal shortening
Dystelephalangy
112500 112600 112700 112SOO 112900 113000 113100 113200 113300 113475 272150 128000
Unless there is an accompanying disorder that produces symptoms, or the shortened digits impair the use of hands and feet, there is no treatment needed for brachydactyly. I will briefly summarize several types of branchydactyly and their properties below.
Types of brachydactyly
The different types of brachydactyly are categorized by the bones and digits affected.
Type A brachydactyly is the shortening of the middle phalanges. These are the finger bones that are the second from the end of each digit. Type A is further classified by finger types. These are as follows:
Type A1: The middle phalanges of all the fingers are shortened. Type A2: The index finger and sometimes the little finger are shortened.
Type A3: Only the little finger is shortened.
Type B brachydactyly affects the ends of the index through little fingers. The last bone on each finger is shortened or completely missing. The nails are also absent. The same occurs in the toes. The thumb bones are always intact but often flattened and/or split.
Type C is rare and affects the index, middle, and little fingers. The middle phalanges, as in type A, are shortened, but the ring finger is often not affected and is the longest finger on the hand. Type D brachydactyly is considered to be common and affects only the thumbs. The end bones of the thumbs are shortened but all the fingers are normal.
Type E brachydactyly is a rare form if it is not accompanied by another disorder. It is characterized by shortened metacarpals and metatarsals. These are the bones in the hands and feet that are third and fourth from the end of the digits. The result is small hands or feet.
The hand phenotype in isolated forms of brachydactyly allows identification of 11 types, with minimal degrees of phenotypic overlap. Typically, they show an autosomal dominant pattern of inheritance with variable expression and penetrance.The number of syndromic forms of brachydactyly is extensive, and, dictated by current expertise.
Molecular dysmorphology studies the abnormal function of molecules leading to disturbed and impaired development. Molecular analysis of isolated forms of brachydactyly has allowed investigation of the role of certain genes in normal human skeletogenesis and limb formation. For instance, the gene BMPR1B mutation results in cartilage malformation and it is transmitted in a dominant negative manner. The HOXD13 gene mutation results in wide spectrum of limp disorders including branchydactyly (7). CDMP1 gene mutations with loss of function were found in certain types of isolated brachydactyly (8). These genes can be concluded to collectively affect the size and shape of individual bones or group of hand and foot bones. Despite of many finding those shed light on to the field, many further studies are needed to unravel other underlying mechanisms of fine tuning of distal skeletal structures.
There is no specific management or treatment that is applicable to all forms of brachydactyly. Plastic surgery is only indicated if the brachydactyly affects hand function or for cosmetic reasons, but is typically not needed. Physical therapy and ergotherapy may ameliorate hand function. Prognosis for the brachydactylies is strongly dependent on the nature of the brachydactyly, and may vary from excellent to severely influencing hand function. If brachydactyly forms part of a syndromic entity, prognosis often depends on the nature of the associated anomalies.
Вестник Ка^ЖМУ №1-2018
REFERENCES
1 Temtamy SA, McKusick VA. The Genetics of Hand Malformations. - New York: Alan R Liss, 1978. - 219 p.
2 Temtamy SA, Aglan MS. Brachydactyly // Orphanet Journal of Rare Diseases. - 2008. - №2. - P. 96-105.
3 Bell J. On brachydactyly and symphalangism // Treasury of Human Inheritance. - London: Cambridge University Press; 1951. - Vol.5. - P. 21-31.
4 OMIM, Online Mendelian Inheritance in Man http://www.ncbi.nlm.nih.gov/Omim/searchomim.html
5 Winter RM, Baraitser M. The London Medical Database. - Oxford: Oxford University Press, 2006. - 152 p.
6 Zhao X, Sun M, Zhao J, Leyva JA, Zhu H, Yang W, Zeng X, Ao Y, Liu Q, Liu G, Lo WH, Jabs EW, Amzel LM, Shan X, Zhang X. Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome // Am J Hum Genet. - 2007. - №80. - P. 361-371. doi: 10.1086/511387.
7 Polinkovsky A, Robin NH, Thomas JT and al. Mutations in CDMP1 cause autosomal dominant brachydactyly type C [Letter] // Nature Genet. - 1997. - №17. - P. 18-19. doi: 10.1038/ng0997-18.
А. Карака
Гарвардмедициналыцмектебь Бостон, А^Ш
БРАХИДАКТИЛИЯГА ЦАТЫСТЫ СИРЕК КЕЗДЕСЕТ1Н ГЕНЕТИКАЛЫЦ АУРУЛАР
ty^h: рахидактилия (BD) фалангтардыц дамымауыменжэне ая; немесе ;олсауса;тарыныц ;ыск;аруымен сипатталады. Юшкентай санды; гипоплазиядан апаразияга дешнп клиникалы; cneKTpi болады. A3 жэне Д типтерш белек, о;шауланган брахидактилиялардыц эртYрлi тYрлерi сирек кездеседь Брахидактилия о;шауланган немесе KYрделi морфология синдромыныц белИ ретшде пайда болуы mym^^ Генетикалы; кецес отбасында брахидактилия тYрлершiц ту;ым куалауына жэне ауруга тэн симптомдардыц болуы немесе болмауына байланысты ЖYргiзiледi. ЖYргiзiлген зерттеу жумыстарыныц нэтижесшде брахидактилия жайлы эртYрлi физикалы; жэне молекулярлы; мэлiметтер жина;талып жэне осы мэлiметтердi алтеме ретiнде багыттауга болады.
ТYЙiндi сездер: брахидактилия(BD), генетика; ;олдыц жэне ая;тыц ;ыс;аруы; CYЙектiц туа бiткен жет^пеушыжтерь
А. Карака
Гарвардская медицинская школа, Бостон, США
РЕДКИЕ ГЕНЕТИЧЕСКИЕ ЗАБОЛЕВАНИЯ, СВЯЗАННЫЕ С БРАХИДАКТИЛИЕЙ
Резюме: Брахидактилия характеризуется недоразвитием фаланг и укорочением пальцев на руках или ногах. Есть и клинический спектр, начиная от незначительной цифровой гипоплазии и заканчивая аплазией. Он наследуется аутосомно-доминантным образом и уменьшает пенетрантность и переменную экспрессию. Различные типы изолированных брахидактилий встречаются редко, за исключением типов А3 и D. Брахидактилия может происходить либо как изолированная мальформация, либо как часть сложного мальформационного синдрома. Характер генетического консультирования будет зависеть от характера наследования типа брахидактилии и наличия или отсутствия сопутствующих симптомов. Таким образом, этот обзор суммирует физические и молекулярные данные о разных типах брахидактилий.
Ключевые слова: брахидактилия (BD), генетика; нарушения рук; укорочение ноги; врожденные пороки развития костей
UDC 57.088
Sh. Shamiluulu1, U. Djakbarova2
1Department of Computer Science, SuleymanDemirel University, Kaskelen, Kazakhstan, 040900 2Department of Molecular Biology and Medical Genetics, Kazakh National Medicine University named after Asfendiyarov, Almaty, 035000 Department of Molecular Biology and Medical Genetics
IDENTIFICATION OF PATIENTS WITH BREAST CANCER BY USING MACHINE LEARNING ALGORITHMS OVER SCIKIT-LEARN ML FRAMEWORK
In this research study the effect of normalization techniques is examined. The five different supervised machine learning algorithms i.e., KNN, Decision tree, Naive-base, Logistic regression and ANN are used on breast cancer dataset obtained from UCI machine learning repository and their performances are compared. The study reveal that different preprocessing techniques can increase the classification accuracy over 90% where high performance is given to Logistic regression and ANN. The proposed approach can be implemented in a well-known benchmark medical problem with real clinical data forbreast cancer disease diagnosis.
Keywords: Breast cancer, Machine Learning Algorithms, Data Classification, Computer Aided Prognosis and Diagnosis
I - introduction. breast cancer plays an important role. Breast cancer is the most
Presently, the use of artificial intelligence (AI) has become widely common cancer among women, except for skin cancers.
accepted in medical applications. This is manifested by an According to CDC statistics 1 in 8 (12%) women in the US will
increasing number of medical devices currently available on the develop invasive breast cancer during their lifetime. Breast
market with embedded AI algorithms [1]. Such devices are being cancer starts when cells in the breast begin to grow out of control
used cancer diagnosis areas where prognosis and diagnosis of [8]. These cells usually form a tumor that can often be seen on an
