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.

Using a set of synthetic oligonucleotides homologous to broadly conserved sequences in-vitro amplification via the polymerase chain reaction followed by direct sequencing results in almost complete nucleotide determination of a gene coding for 16S ribosomal RNA. As a model system the nucleotide sequence of the 16S rRNA gene of M.kansasii was determined and found to be 98.7% homologous to that of M.bovis BCG. This is the first report on a contiguous sequence information of an entire amplified gene spanning 1.5 kb without any subcloning procedures.

We report the complete thermodynamic library of all 10 Watson-Crick DNA nearest-neighbor interactions. We obtained the relevant thermodynamic data from calorimetric studies on 19 DNA oligomers and 9 DNA polymers. We show how these thermodynamic data can be used to calculate the stability and predict the temperature-dependent behavior of any DNA duplex structure from knowledge of its base sequence. We illustrate our method of calculation by using the nearest-neighbor data to predict transition enthalpies and free energies for a series of DNA oligomers. These predicted values are in excellent agreement with the corresponding values determined experimentally. This agreement demonstrates that a DNA duplex structure thermodynamically can be considered to be the sum of its nearest-neighbor interactions. Armed with this knowledge and the nearest-neighbor thermodynamic data reported here, scientists now will be able to predict the stability (AG') and the melting behavior (AW) of any DNA duplex structure from inspection of its primary sequence. This capability should prove valuable in numerous applications, such as (i) predicting the stability of a probe-gene complex; (ii) selecting optimal conditions for a hybridization experiment; (iii) deciding on the minimum length of a probe; (iv) predicting the influence of a specific transversion or transition on the stability of an affected DNA region; and (v) predicting the relative stabilities of local domains within a DNA duplex.It is well established that under a given set of solution conditions the relative stability of a DNA duplex structure depends on its base sequence (1-4). More specifically, the stability of a DNA duplex appears to depend primarily on the identity of the nearest-neighbor bases. Ten different nearestneighbor interactions are possible in any Watson-Crick DNA duplex structure. These pairwise interactions are AA/TT; AT/TA; TA/AT; CA/GT; GT/CA; CT/GA; GA/CT; CG/GC; GC/CG; GG/CC. The overall stability and the melting behavior of any DNA duplex structure can be predicted from its primary sequence if one knows the relative stability (AG') and the temperature-dependent behavior (Al?, ACp°) of each DNA nearest-neighbor interaction (5, 6).Tinoco and coworkers already have demonstrated the power of this predictive ability with RNA molecules for which they and others have determined the appropriate thermodynamic data (7-11). Unfortunately, comparatively few corresponding studies on DNA oligomers have been performed so that the relevant thermodynamic data required to predict DNA structural stability are rather sparse. The seriousness of this deficiency is dramatized by the fact that investigators attempting to evaluate sequence-dependent structural preferences in DNA molecules have resorted to the use of the more available RNA thermodynamic data. This use of RNA data does not reflect a belief that DNA and RNA are thermodynamically equivalent but rather is born of necessity due to a lack of the relevant DNA thermodynamic data. In fact, available comparisons su...

We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive, but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements – 48% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary novel centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise prior to satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.