HUMAN GENES 3/1/2009 STRUCTURE LOCATION FUNCTIONS

Size: px

Start display at page:

Download "HUMAN GENES 3/1/2009 STRUCTURE LOCATION FUNCTIONS"

Miles Flynn
5 years ago
Views:

HUMAN GENES STRUCTURE LOCATION FUNCTIONS Definition: - a polynucleotide fragment of DNA which encodes synthesis of a specific macromolecule polypeptide or RNA; - a fragment of chromosome which

Organization: GENE represents a mixture of regulatory and coding sequences; (a) proximal regulatory sequences: promoter; enhancer, silencer.

1 HUMAN GENES STRUCTURE LOCATION FUNCTIONS Definition: - a polynucleotide fragment of DNA which encodes synthesis of a specific macromolecule polypeptide or RNA; - a fragment of chromosome which controls phenotypic expression of a trait (morphologic, biochemical or physiologic). Organization: GENE represents a mixture of regulatory and coding sequences; (a) proximal regulatory sequences: promoter; enhancer, silencer. (b) distal regulatory sequences: terminator; site of polyadenilation. (c) coding region: exons; introns. Gene location: - In a specific position (locus) of DNA molecule; - Separated by noncoding sequences - spacers. Borders: - There are no physical borders; - There are only functional borders related to initiation and termination of transcription. 1

2 Length of genes: average 3000bp. ex.: β globine gene 1, 5 kb insulin gene 1, 7 kb catalase gene 34 kb dystrophin gene 2,5 Mb Number of genes: About pairs of genes, 2% of genome, for 50% function is known Chromosome No of genes Length, Mb Chromosome No of genes Length, Mb Chromosome X Y No of genes Length, Mb Classification of human genes by their lenght Distribution of human genes by their length Type Short genes Medium genes Long genes Gigantic genes Supergigantic genes Examples Length of gene, kb Length of mrna, kb No of introns α-globine 0,8 0,5 2 β-globine 1,5 0,6 2 Insulin 1,7 0,4 2 IX th factor of blood coagulation 34,0 2,8 7 Catalase 34,0 1,6 12 Phenilalanindehidroginase VIII th factor of blood coagulation 90 2, , Thireoglobine ~300,0 8,7 36 Dystrophine ~2000,0 16,0 60 Length, kb % of total number < 10 23, , , , ,7 > 500 1,2 Peculiarities of structural human genes - Have a very complex structure: * may have more then one promoter or sites for initiation of transcription; * may have more initiation and STOP codons; * contain regulatory complexes; * mrna may be result of alternative splicing; Peculiarities of structural human genes - Are characterized by precise and complex space and temporal expression : * depending on type of cell; * depending on stage of development; * depending on interaction with internal and external factors. 2

3 Full length Short length Peculiarities of dystrophin gene expression Types Length of mrna, kb Muscle 14 Location of promoter 5' untranscribed end Brain 14 Intron 1 Expression Heart, Skeletal muscles Cortex Hippocampus Brain 14 Intron 1 Purkinje cells 1-Dp71 4,5-4,8 Intron 63 All, except muscles 2-Dp116 5,5 Intron 56 Peripheral nerves 3-Dp40 2,2 All, except muscles Dp140 7,5 Intron44 Neurons in embryo Dp260 Retina Functions of genes: - keep, transmit, express genetic information about : - synthesis of one or several polypeptides; - formation of one or several traits: Levels of gene expression: Rh gene: alleles D (Rh+) and d (Rh-) 1 st level molecular synthesis of a polypeptide 2 nd level cellular synthesis of a functional protein which ensures: formation of cellular structure a metabolic pathway a signaling pathway, etc. 3 rd level organism morphologic, physiologic or biochemical trait Locus 1p Function ensure blood group Rh Important for donor-recipient compatibility during blood transfusion and mother-child Levels of expression of Rh+: I molecular synthesis of acyl-protein Rh II cellular presence of Ag D (Rh) on surface of erythrocytes III organism Rh-pozitiv blood group Levels of expression of Rh-: I molecular absence of Rh acyl-protein II cellular absence of Ag D (Rh) on surface of erythrocytes III organism Rh-negativ blood group PAH gene : alleles >200 Locus 12q.24.1 Function encodes enzyme phenilalanin-hydroxilase responsible for transformation Phe Tyr Important because mutation in gene determine phenilketonuria autosomal recessive disease, with somatic and mental retardation Levels of expression of PAH: I molecular synthesis of phenilalanin-hydroxilase II cellular transformation of Phe in Tyr synthesis of melanin, neural transporters etc. III organism normal pigmentation, normal SNC 3

because mutations may induce Marfan syndrome Levels of

II cellular formation of extracellular matrix III

mutations in FBN1 Molecular effect abnormal fibrillin 1

organism level peleiotropy, decreasing of conjunctive

Bones Blood vessels Ocular Dilatarea rădăcinei aortei

of aorta Aneurism Properties of genes: Replication and

4 FBN1 gene: alleles >400 Locus - 15q21.1 Function encodes synthesis of fibrillin 1 Important because mutations may induce Marfan syndrome Levels of expression of FBN1: I molecular synthesis of fibrillin 1 II cellular formation of extracellular matrix III organism resistance of conjunctive tissue Consequences of mutations in FBN1 Molecular effect abnormal fibrillin 1 Cellular effect abnormal extracellular matrix Effect at organism level peleiotropy, decreasing of conjunctive tissue in several systems. Bones Blood vessels Ocular Dilatarea rădăcinei aortei Arachnodactylia Normal function of valves MS: dilatation of aorta Aneurism Properties of genes: Replication and repair Specificity Dosage Stability Interaction with envirnment Pleiotropy Variability Properties of genes: 1. Replication, repair 4

5 2. Specificity: - encodes a specific molecule; - encodes a specific trait; 3. Dosage in phenotype a specific quantity of final product is synthesed; 4. Stability during multiple generations: - But may be unstable genes genes for Ig.; genes for receptors, genes for interaction with environment. 5. Genes have permanent interaction with environment (internal genetic nad external non-genetic): - Factors may change gene expression;!!! The same trait may have different expression in different persons depending on environment. 7. Variability Genes may have several molecular forms polyallelism: 6. Pleiotropy Primary pleiotropy (ex. Marfan syndrome) is determined by multiple action of protein; Secondary pleiotropy (ex. anemia HbS) determined by secondary consequences of effects of mutant protein. - mutations changed sequence new variants of gene alleles Ex. AB0 system a pair of loci on chromosome 9 with different alleles A1, A2, B şi O - Multiple alleles determine several variants of the trait; - A trait controlled by several alleles polymorphic trait; - 25% of human genes have multiple alleles. Classification of human genes Classification of human genes 2. Depending on place of activity: 1. Depending on final product: 1 st class genes for rrna 2 nd class genes for mrna and proteins 3 rd class genes for trna and rrna active in all cells active in specific tissues 3. Depending on stage of development permanently active active during prenatal development active during pubertal development active only in adults 5

6 4. Depending on interaction with environment stabile genes instable genes Require specific condition for expression (Hb S); Silent genes gene for collinesterase during anesthesia with specific drugs respiratory break; Genes with individual specific expression; * There are genes with non-complete penetration. 5. Depending on level of expression: normomorphic isomorphic hypomorphic hypermorphic amorphic neomorphic 6. Depending on number of copies per genome; single-copy genes repetitive genes 7. Depending on the function of final products: - Enzymes - 31,2%; - Modulators of protein synthesis - 13, 6 % - Receptors; - Transcription factors; - Proteins of intracellular and extracellular matrix; - Membrane transporters; - Signaling proteins; - Hormones; - Ig. 50% Location of genes: - genes are located on chromosomes; - each gene has a specific location locus: in identical loci of homologus chromosomes allele genes; in different loci non-allele genes; -Genes of a chromosome linkage group; -Genes of o chromosome located very close represent haplotype, a group of genes which may have common regulatory regions effect of position; Location of genes: - Distribution of genes is randomized: there are chromosomes with high or low density; there are fragments of chromosomes with high or low density; - Some genes are members of repetitive or non - repetitive families; 6

7 - Genes located in autososmes are responsible for autosomal traits, are inherited not depending on gender; - Genes located on gonosomes are responsible for sex-linked traits which are inherited specifically by genders: X-linked traits; Y-linked traits (holandric) Allele and non-allele genes Allele genes: Genele alele: - Located in identical loci in homologous chromosomes; - Responsible for a trait or alternative variants of the trait; -May have several alleles polyalellism; - a person may contain 2 alleles or 1 allele genes on X or Y in men; - în cazul heterozigoţiei (gene alele diferite) se manifestă alela cu o activitate mai mare: - sunt alele cu activitate moderată normomorfe; - sunt alele cu activitate mărită hipermorfe; - sunt alele cu activitate mică hipomorfe; - sunt alele neactive amorfe; - sunt alele cu funcţie nouă neomorfe. - efectul fenotipic al genei depinde de genotip, de interacţiunile alelice, interacţiunile nealelice şi factorii de mediu; Allele genes: -Segregate during meiosis, -During fecundation are distributed randomly and ensure segregation of traits Mendel s laws; -Each person has one maternal and one paternal allele; if alleles are identical homozygote ; if alleles are different - heterozygote. - AA or aa homozygote - Aa heterozygote - X A Y or X a Y hemizygote Non-allele genes: - Located in different loci; - Are responsible for different traits; - Are inherited: linked if are located on the same chromosome (linkage group or haplotype); independently if they are located on diffeent chromosomes; - Their expression is: independent; may be effect of position; may be non-allele interactions; may cooperate in complex traits. 7

8 Genetic map distribution of genes in chromosome, relative distance depends on % of recombination (crossing-over); 1% c-o = 1cM 8

DNA Evolution of knowledge about gene. Contains information about RNAs and proteins. Polynucleotide chains; Double stranded molecule;

DNA Evolution of knowledge about gene. Contains information about RNAs and proteins. Polynucleotide chains; Double stranded molecule; Evolution of knowledge about gene G. Mendel Hereditary factors W.Johannsen, 1909 G.W.Beadle, E.L.Tatum, 1945 Ingram, 1957 Actual concepts The gene hereditary unit located in chromosomes Hypotheses One