Papers by Anne Lykkebo Olsen
Nature, 2004
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-... more Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G1C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.
Nature, 2001
The human genome holds an extraordinary trove of information about human development, physiology,... more The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Nature, 2001
The human genome is by far the largest genome to be sequenced, and its size and complexity presen... more The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature, 2004
Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal dupli... more Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.
Genomics, 2001
Modifier-of-deafwaddler (mdfw) and waltzer (Cdh23v) are loci on mouse chromosome 10 encoding fact... more Modifier-of-deafwaddler (mdfw) and waltzer (Cdh23v) are loci on mouse chromosome 10 encoding factors that are essential for the function of auditory hair cells. The BALB/cByJ-specific mdfw allele encodes a necessary and sufficient modifier that induces progressive early onset hearing loss in CBy-dfw2J heterozygotes. Recessive mutations in the waltzer locus result in circling behavior and congenital deafness. In this report we present a high-resolution integrated genetic and physical map of mdfw and Cdh23v. Our genetic analyses localize mdfw between markers D10Mit60 and 148M13T7 within a 1.01-cM region. The Cdh23v critical interval is fully contained within the mdfw region and localizes between markers 146O23T7 and 148M13T7 within a 0.35-cM interval that is represented in an ≈500-kb BAC contig. Our data suggest that mdfw and Cdh23v are allelic.
Genomics, 2001
Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19... more Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.
Genomics, 1996
Receptor type protein tyrosine phosphatase sigma the human and the mouse genes [93% amino acid se... more Receptor type protein tyrosine phosphatase sigma the human and the mouse genes [93% amino acid se-(PTPRS), a member of a subfamily of receptor type quence identity ( )], a murine cDNA of Ptprs was used protein tyrosine phosphatases, has been mapped to as a hybridization probe for the genetic mapping of the human chromosome 19p13.3 using fluorescence in situ human homologue. A biotinylated probe from the cDNA hybridization (FISH) analysis. Hybridization analysis construct pEX26/33, corresponding to the region encodof chromosome 19 library cosmids has revealed several ing the entire mouse extracellular domain from nucleopositive clones that are part of a contig located in the tides 1 to 3826 (17), was used in FISH analysis as same region. The location of this contig was verified previously described (3 and references therein). This since one of the cosmid clones is anchored to a highprobe was hybridized to human metaphase chromoresolution FISH map of human chromosome 19p. In somes, and a total of 100 chromosomal spreads were addition, the location of this gene relative to preanalyzed. In 10 cases a double staining signal indicaviously mapped proximal markers reveals a new point tive of positive staining was detected and assigned to in the human-mouse synteny map by extending the chromosome 19p13.3 (Fig. ). DAPI staining was used
Cytogenetic and Genome Research, 1993
We have used the fluorescence in situ hybridization (FISH) technique to refine the localization o... more We have used the fluorescence in situ hybridization (FISH) technique to refine the localization of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on human chromosome 7. The result shows that the gene is most likely located within band q31.3.
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Papers by Anne Lykkebo Olsen