Front Matter

Pinpointing Critical Steps Where the Autistic Brain Emerges 33

every neuronal cell as transcription occurs. The tree, with its regularities and
mutations, is a genealogical wonder that is not yet totally understood or ren­
dered predictable. The tree will be better comprehended as records of muta­
tions are assembled that document errors in DNA replication as new cell
divisions occur. The rate of mutation may well be more rapid in cases of expo­
sure to agents not available in most centuries of world history, including syn­
thetic chemicals to which many of us are subjected to repeatedly. It is logically
apparent that every cell could have a personal genomic fingerprint; when these
cellular genealogical trees are better understood, insights regarding ASD and
other health conditions will emerge. Because each mutation can potentially
reveal a cell’s developmental ancestry record, a lineage tree could be con­
structed and developmental patterns noted. Scientists from MIT and Harvard
have carried out whole‐genome sequencing of single cells to demonstrate how
these processes unfold in the brains of human adults [87]. This methodological
approach holds promise in terms of resolving perplexing biological and medi­
cal questions [104]. These investigators evaluated 36 single neurons taken from
the prefrontal cortex of three normal human adults (15, 17 and 42 years of age),
with no known brain disease, to assess whether these neurons had developed
single nucleotide variants or SNPs (Figure 1.18). Since in the adult human
brain, neurons do not divide or regenerate (except in a part of the amygdala
and in the olfactory bulb, see Chapter 5), an examination of accumulated muta­
tions in the brain would be revealing. The MIT and Harvard researchers found
such mutations, in fact over 1,000 mutations per cell [106]. They found that
most of these mutations were unique to a particular cell. They observed promi­
nent mutation rates at specific areas of the DNA (i.e., DNase I hypersensitivity
sites and at transcribed loci). This suggests that even nondividing cells
are  vulnerable to mutation. These are likely introduced to the adult brain

15 Yr 17 Yr 42 Yr

Figure 1.18 The sample sequencing alignment tracks were derived from one of the three
brains on which the study was based (15, 17 and 42 year old normal male brains). A single
nucleotide mutation appears uniquely in the 15 year old brain (shaded area, C7), and one
single nucleotide mutation is displayed in the 17 year old brain, between neurons 2 and 77
(shaded area); however, this is nearly absent from the heart, and from other single cells as
shown in the 42 year old brain (shaded area, c10). Source: Adapted from Ref. [106].