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1. Lactase
Persistence
By
JIGISHA PARMAR 22MBC014
SIMRAN KUMARI 22MMB037

2.  Most people worldwide stop producing
intestinal lactase in childhood, after which
they are unable to digest lactose, the sugar
found in milk.
 Drinking fresh milk causes discomfort and
diarrhea.
 Persistence of intestinal lactase correlates
very closely across the world with agricultural
practice.
 Populations that keep dairy animal have high
levels of persistence, whereas persistence is
rare in those that do not.

3.  For example, whereas the majority of
African adults are lactose-intolerant, the
Beja, Tutsi, and Fulani, who are
traditionally pastoralist, are mostly
tolerant.
 Biochemical and genetic evidence
suggested that the main genetic
determinant of persistence was linked to
the lactase (LCT) gene on 2q21, but no
relevant change could be found in the
coding exons or promoter.

4. • Eventually a single C/T SNP in intron 13 of the
unrelated but neighboring gene MCM6 was
shown to be perfectly associated with
persistence in Northern Europeans.
•Functional assays confirmed that this
polymorphism, –13910 C/T, affected transcription of
the lactase gene.
In Africans, however, no such association could be
demonstrated.
•The –13910 T allele that determines persistence in
Northern Europeans is rare or absent in lactose-
tolerant Africans.

5. •Instead, other SNPs in the same intron
13 of the MCM6 gene are associated
with lactase persistence and have been
shown to affect levels of transcription of
the LCT gene.
•It is interesting to speculate that, had
these effects been found in a
genomewide association study, and if we
were unaware of the function of the LCT
gene, MCM6 might have been the gene
for lactase persistence.

6.  Lactose intolerance is the ancestral
state, in man and other mammals.
 Tolerance has been strongly selected for
in pastoralist populations because of the
obvious advantages of being able to use
milk, a rich source of energy and
nutrients.
 The selection has resulted in convergent
evolution of the trait, with different
sequence variants being selected in

7.  Signals of selection for persistence of
intestinal lactase in pastoralist
populations. Individuals were chosen
who were homozygous for SNP alleles
that determine persistence or non
persistence of intestinal lactase in their
population.
 Each individual was then typed for about
100 SNPs extending over the region
surrounding the functional SNP.
Horizontal lines show the distance over
which each individual was homozygous
for all SNPs; that is, the size of the
conserved haplotype carrying the
functional variant

8. Figure :. (A) Africans homozygous for the C
(persistence, red) or G (nonpersistence, blue) allele at
the –14010 G/C SNP.

9.  B) Eurasians homozygous for the T(persistence,
green) or C (nonpersistence, orange) allele of the –
13910 C/T SNP. Positions are relative to the start
codon of the lactase gene

10.  The haplotypes that carry the persistence
alleles are very much longer than those
associated with nonpersistence .
 In Europians, the average fully homozygous
tract length in –13910 T/T homozygotes was
1.4 Mb, in comparison with 1900 bp in C/C
homozygotes; in Africans lengths were 1.8 Mb
and 1800 bp in –14010 C/C and G/G
homozygotes, respectively.
 The very long haplotypes are evidence of
strong recent selection: there has been little
time for recombination to fragment them.

11. THANK YOU