EREDITATE -

CONSERVAREA CARACTERELOR PARENTALE - SUB INFLUENTA FACTORILOR DE MEDIU

SUPORTUL MOLECULAR AL EREDITATII

MENDEL- 1865- notiunea de FACTOR EREDITAR

GRIFFITH- 1928 efectul transformant al capsulei polizaharidice de diplococus pneumoniae

AVERY, CARTY, MacLEOD, 1944 ADN FACTOR TRANSFORMANTMODEL EXPERIMENTAL PE SOARECI INOCULATI CU TULPINI DE DIPLOCOCUS PNEUMONIAE: (VIRULENTE- S, NEVIRULENTE- R) 1) AMESTEC TULPINI R CU PROTEINE DIN TULPINI S 2) CULTIVAREA FORMEI R CU ARN DIN TULPINI S 3) CULTIVAREA TULPINII R CU CAPSULA MUCOPOLIZAHARIDICA DIN TULPINA S4) CULTIVAREA TULPINII R CU ADN EXTRAS SI PURIFICAT DIN FORMELE S AU APARUT COLONII VIRULENTE CARE INJECTATE LA SOARECI AU PROVOCAT MOARTEA ACESTORA 5) CULTIVAREA FORMELOR VII R CU ADN S DISTRUS IN PREALABIL CU ENZIME- DN-AZA- SE OBTIN FORME R NECAPSULATE SI NEVIRULENTE

CONCLUZIE: ADN ESTE SUPORTUL EREDITATII

CARACTERE ADN - IMPLICATIA IN EREDITATE ARE STRUCTURA SPECIFICA SPECIFICITATE DE SPECIE PRIN ORDONAREA BAZELOR AZOTATE.

ARE CAPACITATE DE SINTEZA ( AUTOREPLICARE).

INFORMATIA ADN POATE FI DECODIFICATA SI TRANSMISA ARN SINTEZA DE PROTEINE CARACTERE.

ESTE SURSA DE VARIABILITATE PRIN RECOMBINARE SI MUTATIE.

ARE O DISPUNERE LINIARA, INFORMATIA DETINUTA FIIND ACCESIBILA.

STRUCTURA ADN LOCALIZAREA CELULARA A ADN :-NUCLEU 98% CITOPLASMA- MITOCONDRIE 2%

STRUCTURA PRIMARA : MACROMOLECULA CU GRAD INALT DE POLIMERIZARE.

UNITATEA STRUCTURALA = NUCLEOTIDUL ( BAZA AZOTATA + PENTOZA+ REST DE FOSFAT ANORGANIC)

DNA Building BlocksNitrogenous BasePentose SugarTriphosphate5 Phosphate3 Hydroxyl

Nitrogenous Base StructurePurines Double Ring Bases(A and G)Pyrimidines Single Ring Bases(T and C)

NUCLEOZIDUL = BAZELE AZOTATE LEGATE la C1 AL DEZOXIRIBOZEI Ex: ADENOZINA, GUANOZINA, CITIDINA, TIMIDINANUCLEOZIDUL SE LEAGA PRIN C5 AL DEZOXIRIBOZEI DE ACIDUL FOSFORIC

POLIMERIZAREA SE FACE PRIN LEGATURI 3- 5 FOSFODIESTERICE INTRE C3 AL DEZOXIRIBOZEI SI POZITIA C5 A NUCLEOTIDULUI URMATOR-

SE REALIZEAZA O CATENA GLUCIDO FOSFORICA IN CARE DEZOXIRIBO-NUCLEOTIDELE ALTERNEAZA CU GRUPAREA FOSFAT- PE ACEST SCHELET SE ASEAZA BAZELE AZOTATE.

FIECARE LANT POLINUCLEOTIDIC SE TERMINA CU O GRUPARE 5 FOSFAT RESPECTIV 3OH POLARITATE MOLECULEI ADN 35.

DNASugar-phosphate backbone serves as a backbone. The backbone has directionality (PO4 / OH).Bases encode the genetic information.

STRUCTURA SECUNDARA A ADN v- 2 CATENE POLINUCLEOTIDICE LEGATE PRIN BAZELE AZOTATE COMPLEMENTARE: A-T si G-C.

LEGATURI PRIN PUNTI DE HIDROGEN DUBLE SAU TRIPLE.

- CATENELE SUNT COMPLEMENTARE SI CODETERMINANTE.

Anti-parallel Bonding5 PO4PO4 5 3 OH3 OH

DOVEZI EXPERIMENTALE ALE STRUCTURII SECUNDARE A ADN

REGULA LUI CHARGAFF- BAZA RATIO A+T/G+C 1

The First Clues to DNA Structure G A T C22.1%28.1%30.1%19.7%15.4%33.6%37.1%13.940.4%9.0%11.7%38.9%8.9%42.6%39.9%8.6%

PRINCIPIUL DENATURARII SI RENATURARII ADN

(PRIN TEMPERATURI MARI(95 GRADE CELSIUS)/ MEDIU ALCALIN).

Denaturation / Renaturation The bonds that hold DNA strands together are easily broken and reformed.

DOVEZI EXPERIMENTALE ALE STRUCTURII SECUNDARE A ADNIMPORTANTA:

-CAPACITATE DE AUTOREPLICARE;-CONSERVAREA INFORMATIEI GENETICE;TRANSCRIPTIE.

- APLICATII- BIOLOGIA MOLECULARA.

Polymerase chain reaction (PCR)

Alfred Hershey and Martha Chase (1952) DNA is genetic material.Watson and Crick (1953) DNA is a double helix.The Big Bang

STRUCTURA TERTIARA A ADN

FORME FIZICE ALE ADNADN TIP A - DEXTROGIR, SPIRE MAI APROPIATE, DEPRESIUNILE SUNT DISPUSE OBLIC REVERSIBIL CU FORMA B

ADN TIP B- APARE IN INTERFAZA- G1+S

ADN TIP Z- LEVOGIR, SCHELETUL GLUCIDO FOSFORIC ESTE NEREGULAT(ZIG- ZAG ), GUANINA ESTE LA EXTERIOR FIXEAZA RAPID SI STABIL SUBSTANTA CHIMICE CANCERIGENE

From A to Z DNA

CLASIFICAREA ADNIN RAPORT CU STRUCTURA PRIMARA - REPETITIV - NEREPETITIV

DUPA STRUCTURA TERTIARA

DUPA TOPOGRAFIA INTRACELULARA NUCLEAR - MITOCONDRIAL

ADN NUCLEARCANTITATEA DE ADN NUCLEAR NU ESTE DIRECT PROPORTIONALA CU GRADUL DE EVOLUTIE A SPECIEI

NU EXISTA O CORELATIE NUMAR GENE CANTITATE ADN EXPLICATIA: GENOMUL UMAN ARE 30000 GENE CE CONTROLEAZA CARACTERE CELULARE SI INDIVIDUALE

MECANISMUL DENATURARII / RENATURARII SI HETEROGENITATEA SECVENTELOR ADN CROMOZOMAL

ADN REPETITIVESTE NONINFORMATIONAL

INALT REPETITIV- 10-15% DIN GENOMUL CELULAR UNITATEA REPETITIVA ARE O SECVENTA DE 5-10 NUCLEOTIDE REPETATE 105-107/ POT FI MAI MULTE SECVENTE DIFERITE RENATUREAZA RAPIDNU EXISTA IN CROMOZOMUL Y NU SE TRANSCRIU IN ARNm ROL DISCUTABIL IN PROTECTIE SAU ORGANIZARE

ADN REPETITIVMODERAT REPETITIV-25-30% DIN ADN CELULAR COEFICIENT DE REPETABILITATE DE 103-10-4 SECVENTA REPETITIVA 150-300 PERECHI DE NUCLEOTIDEINTERCALAT INTRE SECVENTELE NEREPETITIVE ARE ROL REGLATOR IN GENOMUL CELULAR LOC DE FIXARE PENTRU MOLECULELE IMPLICATE IN TRANSCRIPTIE EXISTA SECVENTE GENETIC ACTIVE- HISTOGENE, ARNt,ARNr.

PALINDROMUL

SECVENTA PARTICULARA DE ADN REPETITIVARE SIMETRIE ROTATIONALAFORMAT PE PRINCIPIUL COMPLEMENTARITATII CU BUCLE CATENARE ARE LUNGIME VARIABILA 6-12 NUCLEOTIDE STRUCTURA CU ASPECT DEAC DE PARPOATE CONTINE TRANSPOZONI ( GENE SARITOARE)IN GENOM EXISTA 120000 DE PALINDROAMEROL- RECUNOASTE ENZIMELE IMPLICATE IN REPLICAREA ADN SAU IN TRANSCRIPTIE ESTE RECUNOSCUT DE ENZIMELE DE RESTRICTIE SE INTILNESTE LA NIVELUL TELOMERELOR.

ADN NEREPETITIV

SUNT SECVENTE UNICE REPREZINTA 50-70% DIN GENOM ALTERNEAZA CU CEL NEREPETITIV DIN CROMOZOM ESTE INFORMATIONAL

GENOMUL MITOCONDRIAL REPREZINTA 1-2% DIN TOTALUL ADN CELULAR

ESTE BICATENAR, IN DUBLU HELIX, CIRCULAR

POATE SUFERI MUTATII

CODIFICA 30 DE GENE STRUCTURALE

DETINE 17000 DE PERECHI DE BAZE

GENE IMPLICATE IN LANTUL RESPIRATOR- CITOCROM b CITOCROM-oxidaza, ATP-aza, 22 GENE PENTRU ARNt SPECIFIC SI ARNr

SINTEZA ACESTOR PROTEINE POATE FI INHIBATA MEDICAMENTOS

NU ARE SECVENTE NONINFORMATIONAL

GENOMUL MITOCONDRIAL SE ASEAMANA CU ADN BACTERIAN

SE REPLICA SEMICONSERVATIV INDEPENDENT DE ADN CROMOZOMIAL AVIND COMPLEX ENZIMATIC PROPRIU PENTRU REPLICARE SI TRANSCRIERE

DETERMINA EREDITATEA MATROCLINA

POATE DETERMINA EXPRESIA FENOTIPICA A UNOR CARACTERE TRANZITORII SAU PERMANENTE

CARACTERELE SUNT DETERMINATE DE PLASMAGENE A CAROR TOTALITATE = PLASMOM MITOCONDRIAL

CRITERII DE IDENTIFICARE A CARACTERELOR MITOCONDRIALE:

REZULTATE DIFERITE DUPA FECUNDATIE CE NU RESPECTA REGULILE

DETECTAREA FACTORILOR EXTRANUCLEARI CE NU RESPECTA SEGREGAREA

DACA SE PRACTICA CONSANGHINIZAREA APAR CARACTERE MATERNE DUPA 2-3 GENERATII

Human Genome Project

Human Genome ProjectGoals: identify all the approximate 30,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA, store this information in databases, improve tools for data analysis, transfer related technologies to the private sector, and address the ethical, legal, and social issues (ELSI) that may arise from the project. Milestones: 1990: Project initiated as joint effort of U.S. Department of Energy and the National Institutes of Health June 2000: Completion of a working draft of the entire human genome February 2001: Analyses of the working draft are published April 2003: HGP sequencing is completed and Project is declared finished two years ahead of scheduleU.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

What does the draft human genome sequence tell us?

By the Numbers The human genome contains 3 billion chemical nucleotide bases (A, C, T, and G). The average gene consists of 3000 bases, but sizes vary greatly, with the largest known human gene being dystrophin at 2.4 million bases. The total number of genes is estimated at around 30,000--much lower than previous estimates of 80,000 to 140,000. Almost all (99.9%) nucleotide bases are exactly the same in all people. The functions are unknown for over 50% of discovered genes.U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

What does the draft human genome sequence tell us? The Wheat from the Chaff

Less than 2% of the genome codes for proteins. Repeated sequences that do not code for proteins ("junk DNA") make up at least 50% of the human genome. Repetitive sequences are thought to have no direct functions, but they shed light on chromosome structure and dynamics. Over time, these repeats reshape the genome by rearranging it, creating entirely new genes, and modifying and reshuffling existing genes. The human genome has a much greater portion (50%) of repeat sequences than the mustard weed (11%), the worm (7%), and the fly (3%).U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

How does the human genome stack up?

Gene number, exact locations, and functions Gene regulation DNA sequence organization Chromosomal structure and organization Noncoding DNA types, amount, distribution, information content, and functions Coordination of gene expression, protein synthesis, and post-translational events Interaction of proteins in complex molecular machines Proteomes (total protein content and function) in organisms Correlation of SNPs (single-base DNA variations among individuals) with health and disease Disease-susceptibility prediction based on gene sequence variation Genes involved in complex traits and multigene diseases Developmental genetics, genomics Future Challenges: What We Still Dont KnowU.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Anticipated Benefits of Genome ResearchMolecular Medicine improve diagnosis of disease detect genetic predispositions to disease create drugs based on molecular information use gene therapy and control systems as drugs design custom drugs (pharmacogenomics) based on individual genetic profiles Microbial Genomics rapidly detect and treat pathogens (disease-causing microbes) in clinical practice develop new energy sources (biofuels) monitor environments to detect pollutants protect citizenry from biological and chemical warfare clean up toxic waste safely and efficientlyU.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Anticipated Benefits of Genome Research-cont.Risk Assessment evaluate the health risks faced by individuals who may be exposed to radiation (including low levels in industrial areas) and to cancer-causing chemicals and toxinsBioarchaeology, Anthropology, Evolution, and Human Migration study evolution through germline mutations in lineages study migration of different population groups based on maternal inheritance study mutations on the Y chromosome to trace lineage and migration of males compare breakpoints in the evolution of mutations with ages of populations and historical events U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Anticipated Benefits of Genome Research-cont.DNA Identification (Forensics) identify potential suspects whose DNA may match evidence left at crime scenes exonerate persons wrongly accused of crimes identify crime and catastrophe victims establish paternity and other family relationships identify endangered and protected species as an aid to wildlife officials (could be used for prosecuting poachers) detect bacteria and other organisms that may pollute air, water, soil, and food match organ donors with recipients in transplant programs authenticate consumables such as caviar and wineU.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Medicine and the New GeneticsAnticipated Benefits: improved diagnosis of disease earlier detection of genetic predispositions to disease rational drug design gene therapy and control systems for drugs personalized, custom drugs U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003Gene Testing Pharmacogenomics Gene Therapy

ELSI: Ethical, Legal, and Social Issues Privacy and confidentiality of genetic information. Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. Psychological impact, stigmatization, and discrimination due to an individuals genetic differences. Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making. Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and qualitycontrol measures.U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

ELSI Issues (cont.) Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease, diabetes, and Alzheimers disease). Fairness in access to advanced genomic technologies. Conceptual and philosophical implications regarding human responsibility, free will vs genetic determinism, and concepts of health and disease. Health and environmental issues concerning genetically modified (GM) foods and microbes. Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials. U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

HapMapAn NIH program to chart genetic variation within the human genome Begun in 2002, the project is a 3-year effort to construct a map of the patterns of SNPs (single nucleotide polymorphisms) that occur across populations in Africa, Asia, and the United States. Consortium of researchers from six countries Researchers hope that dramatically decreasing the number of individual SNPs to be scanned will provide a shortcut for identifying the DNA regions associated with common complex diseases Map may also be useful in understanding how genetic variation contributes to responses in environmental factors

In 2003 scientists in the Human Genome Project achieved a long-sought goal by obtaining the DNA sequence of the 3.2 billion base pairs (the order of As, Ts, Cs, and Gs) making up the human genome. The DNA sequence spells out the exact instructions needed to maintain and reproduce a living organism whether its a person, a plant, or a paramecium.Some fascinating insights so far:- The human genome is almost (99.9%) exactly the same in all people.- Only 2% of the human genome contains genes, the part of DNA that encodes recipes for proteins. We dont know what the remainder does.- We have an estimated 30,000-40,000 genes; the functions remain unknown for more than half of these.- Almost half of all proteins predicted from human genes share similarities with fruit flies and worms, underscoring the unity of life.- MUCH remains to be learned!