2、Chapter 3 Molecular Basis of Genetics

Chapter 3 Molecular Basis of Genetics1、Information content of the human genomeSingle copy DNA: nucleotide sequences present once in the haploid单倍体genome, as are most of those encoding polypeptides in the eukaryotic genome.Repetitive DNA: DNA sequences that are repeated in the genome.①Repetitive DNA Clustered repeated sequences ：various short repeats organized tandemly in a head-to-tail fashion②Dispersed repetitive DNA sequences：dispersed throughout the genome rather than localized.2、Gene organization and structure（1）Structural features of a typical human geneMolecular definition of a gene: a sequence of DNA in the genome that is required for production of a functional product.A gene includes not only the actual coding sequences but also adjacent nucleotide sequence s required for the proper expression of the gene that is, for the production of a normal mRNA molecule①Introns: The majority of genes are interrupted by one or more noncoding regions. These intervening sequences, called introns, are initially transcribed into RNA in the nucleus but are not present in the mature mRNA in the cytoplasm.②The adjacent nucleotide sequences (flanking sequence)⏹Flanking sequence provide the molecular “start” and “stop” signals for the synthesisof mRNA transcribed from the gene.⏹Flanking sequences contain the 5´ and 3´untranslated regions (UTR).⏹At the 5´end of each gene lies a promoter region that includes sequencesresponsible for the proper initiation of transcription. There are several different typesof promoter found in the human genome.⏹Except for promoter, there are some other regulatory elements (located either 5´ or3´of a gene or in its introns) , including enhancers, silencers, and locus controlregions, regulate the transcription process.At the 3´ end of the gene lies an untranslated region of importance that contains a signal for the addition of a sequence of adenosine residues (the so-called polyA tail) to the end of the mature mRNA.（2） Gene familiesMany genes belong to gene families, which share (1) closely related DNA sequences and encode polypeptides with (2)closely related amino acid sequences.（3） Pseudogenes 假基因DNA sequences that closely resemble known genes but are nonfunctional , are called pseudogenes（4） Noncoding RNA genes ——microRNA (miRNA) genescontrol the expression or repression of other genes during development.plays an important role in transcriptional regulation, protein degradation and translocation, chromosome replication, stability and translation of messenger RNA and also in RNA processing and modification. Diseases Caused by Noncoding RNA: Alzheimer’s disease, Hearing loss, Cancer3、Genomic Imprinting ※Genomic imprinting is a phenomenon of epigenetic chromosomal modification in germ cells that leads some genes to be expressed based on their parental origin and causes a developmental asymmetry in the function of parental genomes.Characterisics:（1）occur in the germline of one parent, but not the other（2）It is a reversible form of gene inactivation but not a mutation(2) Characters of genomic imprinting:①Imprinting is a normal process caused by alterations in chromatin that occur in the germline 种系 of one parent, but not the other, at characteristic locations in the genome. These alterations include the covalent modification of DNA, such as methylation of cytosine to form 5-methylcytosine, or the modification or substitution 取代 in chromatin of specific histone types, which can influence gene expression within a chromosomal region.② Notably, imprinting affects the expression of a gene but not its primaryDNA sequence. It is a reversible form of gene inactivation but not a mutation, and thus it is an example of what is called an epigenetic effect 外遗传影响.Disease: Prader-Willi syndrome (PWS) 肌张力减低-智力减低-性腺功能减退-肥胖综合征, Angelman syndrome(AS)( severe mental retardation, hyperactivity, seizures, hypotonia, jerky movements, lack of speech, and frequent smiling and laughter), Ligers and TigonsE x o n I n t r o n T A T A b o x CAATboxGC box EnhancerGenomic ImprintingImprinting takes place12malefemaleadultmaintenance3maintenanceProcess of genomic imprinting:1.Erasure消除2.Establishment3.maintenance在原始生殖细胞中被消除精子卵子中重新出现4、concept of Gene mutation※A change of the DNA sequence within a gene or chromosome.5、the origins of gene mutation※（1）Errors introduced during the normal process of DNA replication, or mutations arising from a failure to repair DNA after damage and to return its sequence to what it was before the damage.（2）Some mutations are spontaneous, whereas others are induced by physical or chemical agents called mutagens, because they greatly enhance the frequency of mutations.6、the types of gene mutation※（1）Nucleotide substitutions (point mutation)●Transition:nucleotide changes that involve the substitution of one purine for the otheror one pyrimidine for the other●Transversion:the replacement of a purine for a pyrimidine因其作用对象不同而产生不同的遗传学效应●Missense mutations：alter the code in a triplet of bases and cause the replacement ofone aa.by another in the gene product●Nonsense mutations:cause the replacement of the normal codon for an amino acid byone of the three termination codons,converts a coding exon into a termination codon causes translation to stop partway（2）Deletions and insertions●Insertions: adding a piece of DNA.●Deletions: removing a piece of DNA.●Frameshift mutations:This type of mutation occurs when the addition or loss of DNAbases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that code one amino acid each. A frameshift mutation shifts the grouping of these basesand changes the code for amino acids. The resulting protein is usually nonfuncitonal.Insertions, deletions can all be frameshift mutations. changes a gene's reading frame.insertions,deletions can all be frameshift mutations（3）Dynamic mutationsNucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated.This type of mutation can cause the resulting prote in to function improperly. (eg. Huntington’s Disease )A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated.。