Human genome


Consists of approximately 34,000 genes.

Three billion nucleotides of DNA.

DNA nucleotides organized into 23 pairs of chromosomes.

Genes are sequences of DNA that are transcribed into RNA and translated into proteins.

Distinct functional proteins exceeds 100,000.

More than 80 million genetic variants, most of which no understanding of their role in clinical disease.

More than 99% of the human genome is identical from one person to the next.

Less  than 1% of the genome that differs among people includes variants that influence physical characteristics and health.

Each human genome contains approximately 3-5, million variants, including approximately 30,000 variants in protein coding genes, when compared with a reference gene.

The genome is unstable and natural selection requires genetic fidelity and diversity.

All cells contain the same DNA.

Allele frequency is defined as the proportion of alleles, two per individual, that carry a particularly varied and specific location in the genome.

Gene expression is customized to the specific cell type and physiologic stimulus.

These complex gene expression patterns controlled by genes enhancers, which are short, non-coding regions of DNA that recruit transcription factors required for junior activation nearby protein coding genes.

Humans differ on approximately 0.8% of their genome.

Humans inherit two copies of each gene, one copy from each parent.

Rare genetic diseases are often follow Mendelelian inheritance patterns, in which the disease is the direct result of a single gene mutation.

Diseases that follow an autosomal dominant inheritance pattern require only one mutant allele. and typically affect every generation of the family.

Mendelian diseases are typically rare, and causal genetic variants are also rare because they often reduce reproductive fitness, and are less likely to be passed on over generations.

If a variant is common in the general population, it is unlikely due causal of disease decreases reproductive fitness.

Autosomal recessive diseases require the inheritance of two mutant alleles, which often results in asymptomatic or mildly symptomatic carriers such as Frederic’s ataxia, Tay-Sachs disease.

X-linked diseases are more commonly observed in men because they only have a single X chromosome, while women can be asymptomatic or mildly symptomatic carriers.

Spontaneous mutations are not inherited, but occur during development because of DNA replication errors.

The phenotypic severity of a genetic mutation depends on how the DNA sequence is altered: point mutations occur when a single nucleotide is changed and can result in silent, missense, or nonsense mutations.

Silent mutations, are asymptomatic, and do not affect the encoding proteins because the mutated DNA sequence still codes for the wild type amino acid.

Missense mutations change a specific amino acid within a protein, and the phenotypic severity depends primarily on how the amino acid alters the proteins function.

Missense alterations in DNA sequence can be synonymous, which means that a different nucleotide sequence leads to no change in amino acid sequence, or nonsynonymous.that a different nucleotide sequence leads to a change in amino acid sequence.

A nonsense mutation results in a stop codon that terminates the translation of messenger RNA into protein.

The severity of nonsense mutations depends on where in the protein the stop codon occurs, but often results in severely truncated proteins.

Somatic and germline mosaicism can occur when mutations occur in later stages of development such that only certain cell lineages are affected by the mutation, while other cell and tissue types remain normal.

Mosaicism result in diverse phenotypes, depending on where in the development process the mutation occurs.

Mosaicism can be observed in heterozygous females with X-linked mutations because X-inactivation randomly silences either the wild type or mutant X chromosomes in each cell.

Approximately 2.4 million DNA copy number variations, genetic sequences the difference in number of copies in the human genome, mapping to approximately 200,000 unique loci that cover 72% of the human genome.

Copy number variation’s contribute to an individual variations in a wide variety of traits influencing the transcriptome.

Copy number variation’s are associated with complex disorders, particularly developmental delay and intellectual disability and can impair adaptive behavior in every day life.

Contains several million individual DNA sequence variants, alleles, defined as differences in sequence at identical sites on homologous chromosomes.

Accounts for about 1.8% of the 3 Gb haploid genome.

Estimated 7 million base pairs that vary between individuals are inherited as units referred to as haplotypes.

Haplotype map analysis reveals that vast majority of common variations in the 3 billion base pairs can be reduced to 250,000 for those of European and Asian ancestry and 500,000 for those of African ancestry, and these DNA segments or haplotype bins indicate the tagging of variations that influence a disease or trait.

Less than 2% codes for proteins.

DNA sequences are typically conserved across species.

More than half represents blocks of repetitive nucleotide codes with unknown functions.

Whole-genome studies indicate that the encoding function gene of DNA accounts for only 2% of the whole genome, and the non-coding DNA represents most of the genome.

Noncoding RNA is the product of noncoding DNA transcription.

Noncoding RNA is divded into : long-chain, medium chain, and short chain noncoding RNA.

Long-chain noncoding RNA functions include transcription interference, gene splicing, transcription regulation, genomic imprinting, X-chromosome inactivation, cell-cycle regulation, dyeing modification, gentic modification and immune response.

Many alleles are common and encode functional differences in protein variants such as €2, €3 and €4 variants of apolipoprotein E, conferring a different risk for the development of Alzheimer’s disease.

Single nucleotide gene polymorphisms (SNPs) inherited in Mendelian manner.

SNPs occur approximately every 300-500 base pairs and account for a significant diversity in the genome.

Genetic diversity among cells appears in chromosomal and structural variants.

Loss of the Y chromosome can be detected in almost half of men who are older than 70 years of age and sub chromosomal rearrangements can be detected in 2-3% of older adults.

The single nucleotide polymorphismis the most common form of DNA variation in the human genome and typically are biallelic, and they may occur anywhere in the genome within exons, introns, or intergenic regions.

Genome-wide association studies can survey the entire genome to elucidate susceptibility to comon heritable diseases.

Genome-wide association studies can quantify the association between the presence of disease and genetic variation at known positions in the genome, which is the single-nucleotide polymorphisms.

Genome-wide association studies can pinpoint relatively small areas of the genome that may contribute to the risk of disease.

There are millions of known SNP’s occurring in known locations across the entire genome.

The associated SNP’s mark a region of the human genome that influences the risk of disease.

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