Jax Labs eBook - 17


created divergent substrains when they
obtained descendants of C57BL/6J
mice and bred them in seclusion. This
limitation, driven by genetic drift, often
contributes to unexpected phenotypes
and hampers the reproducibility of data
generated with laboratory mice. Although
most mutations go unnoticed, some occur
in genes that affect a mouse's appearance
or physiology (Reardon, 2017). Therefore,
the genomic sequences of B6 substrains
are different from the corresponding
Reference Genome Sequences.
In very simple terms, a Reference
Genome Sequence for any given organism
is the complete and ordered "assembly"
of DNA, as denoted by the nucleotides A,
T, C, and G. Reference genome sequences
result from the de novo sequencing
and assembly of a haploid complement
of an organism's genome. A reference
genome is the initial sequence to which
all subsequent sequences are compared
but it is often incomplete mainly due
17 | GENengnews.com

to technical constraints. The human
and mouse gene catalogues remain
imperfect. Both genome sequences are
still incomplete. Some authentic genes
are missing, fragmented, or otherwise
incorrectly described, and some predicted
genes may be in fact pseudogenes.
The first mouse reference genome,
fully sequenced in 2002, contained
approximately 24,500 protein-coding
genes distributed across 19 pairs
of autosomes, plus the X and Y sex
chromosomes. Research groups around
the world rely on reference sequences for
much of current genetics research, as
well as for designing and validating new
mouse models built using specific genetic
The goal of reference genomes is to
provide the most accurate and complete
representation of specific genomes by
correcting errors, closing gaps, finding
ways to represent difficult regions such
as centromeres, and capturing genetic
variation (McGarvey et al., 2015). Since the
completion of the Mouse Genome Project

in 2002, the mouse reference genome
has continued to be updated and refined
by the Genome Reference Consortium
(GRC), a team of scientists from several
institutions in Europe and in the United
States. The GRC periodically reannotates
the mouse genome as the C57BL/6J
assembly is updated, the annotation
pipeline software is further improved on,
or as additional data become available.
The Genome Reference Consortium
Mouse Build 38 patch release 6 (GRCm38.
p6) is the latest version released in
September 2017 representing the
C57BL/6J strain. Despite being one of
the highest quality mammalian genome
assemblies ever produced, it still has
more than 600 gaps and includes
suboptimal representations for some
genes. GRCm38 still contains 523 gaps
within chromosome sequences, and there
are nearly 300 unresolved issues that
have been reported to the GRC (Sarsani et
al., 2019). In addition to gaps, these issues
include reports of localized sequence
mis-assembly, missing genic and

https://www.jax.org/strain/000664 https://www.ncbi.nlm.nih.gov/grc https://www.ncbi.nlm.nih.gov/grc http://www.informatics.jax.org/mgihome/homepages/stats/all_stats.shtml http://www.informatics.jax.org/mgihome/homepages/stats/all_stats.shtml https://www.ncbi.nlm.nih.gov/assembly/GCF_000001635.26 https://www.ncbi.nlm.nih.gov/assembly/GCF_000001635.26 http://www.GENengnews.com

Jax Labs eBook

Table of Contents for the Digital Edition of Jax Labs eBook

Jax Labs eBook - 1
Jax Labs eBook - 2
Jax Labs eBook - 3
Jax Labs eBook - Contents
Jax Labs eBook - 5
Jax Labs eBook - 6
Jax Labs eBook - 7
Jax Labs eBook - 8
Jax Labs eBook - 9
Jax Labs eBook - 10
Jax Labs eBook - 11
Jax Labs eBook - 12
Jax Labs eBook - 13
Jax Labs eBook - 14
Jax Labs eBook - 15
Jax Labs eBook - 16
Jax Labs eBook - 17
Jax Labs eBook - 18
Jax Labs eBook - 19
Jax Labs eBook - 20
Jax Labs eBook - 21
Jax Labs eBook - 22
Jax Labs eBook - 23
Jax Labs eBook - 24
Jax Labs eBook - 25
Jax Labs eBook - 26
Jax Labs eBook - 27
Jax Labs eBook - 28
Jax Labs eBook - 29
Jax Labs eBook - 30
Jax Labs eBook - 31
Jax Labs eBook - 32
Jax Labs eBook - 33
Jax Labs eBook - 34
Jax Labs eBook - 35
Jax Labs eBook - 36