The Importance of High Quality Finished Sequence

Lessons to be drawn from the preceding section are that: (1) reliable sequence information is essential for interpreting the structures of deletions and other rearrangements involving

Fig. 2. Classical AZF deletions mapped onto the finished Y chromosome sequence. (Top) Approximate locations of the AZFa and AZFc deletion intervals on the Y chromosome. (Middle) Visualization of duplicated sequences with greater than 900 bp of identity in inverted (upper middle) and direct (lower middle) orientation on the Y chromosome-specific euchromatic reference sequence. This image was generated using the GenAlyzer software (43) and places diagonal lines between aligned chromosomes to show the location of inverted and direct repeats. Underneath the inverted repeats are shown the eight palindromes identified within the Y sequence. The visualization of direct repeats is annotated with the positions of the repeats promoting the AZFa and AZFc deletions, HERV-HERV and b2/b4 elements, respectively. (Bottom) Expanded view of the AZFc region and adjacent sequences, showing the mosaic of smaller repeats referred to in the text and including the nonrepeated segment u3 that contains 50f2/C.

Fig. 2. Classical AZF deletions mapped onto the finished Y chromosome sequence. (Top) Approximate locations of the AZFa and AZFc deletion intervals on the Y chromosome. (Middle) Visualization of duplicated sequences with greater than 900 bp of identity in inverted (upper middle) and direct (lower middle) orientation on the Y chromosome-specific euchromatic reference sequence. This image was generated using the GenAlyzer software (43) and places diagonal lines between aligned chromosomes to show the location of inverted and direct repeats. Underneath the inverted repeats are shown the eight palindromes identified within the Y sequence. The visualization of direct repeats is annotated with the positions of the repeats promoting the AZFa and AZFc deletions, HERV-HERV and b2/b4 elements, respectively. (Bottom) Expanded view of the AZFc region and adjacent sequences, showing the mosaic of smaller repeats referred to in the text and including the nonrepeated segment u3 that contains 50f2/C.

repeated Y regions; (2) the sequence should be based on the Y chromosome of a single man in order to avoid confusion between polymorphisms and variants in different copies of repeated sequences within the same chromosome; but (3) sequence may be needed from more than one individual in order to understand the extent of normal polymorphic variation. The first two of these requirements have largely been met by the near-complete euchromatic sequence reported by Skaletsky et al. (1), which the authors estimated had an error rate of less than 1 in 10,000 bases, and was mostly obtained from bacterial artificial chromosomes derived from a single individual, the RPCI-11 donor. Exceptions, however, included nine clones spanning the AZFa region. Relevant details of the AZF region sequences are discussed next. Here, we note that approx 25% of the euchromatic Y sequence is made up of eight palindromes (the largest spanning 2.9 Mb; Figs. 2 and 3) with arm-to-arm sequence identities of 99.94-99.997%.

Although AZFa is made up of unique sequence, much of AZFb consists of palindromes and AZFc is made up almost entirely of such sequences. Only 27 proteins were identified as being encoded by the male-specific portion of the Y, but many of these have multicopy genes. In addition, the male-specific portion of the Y contains 28 non-coding transcripts, again many with multicopy genes. Genes coding for 14 different proteins lie in the AZF regions.

Was this article helpful?

0 0

Post a comment