SNP homozygosity mapping of alpha-mannosidosis family. The image is demonstrating three shared homozygous regions (red bars) which is a homozygosity by descent (HBD) on chromosome 16 and 19.
Alpha-mannosidosis family pedigree presenting the homozygous region in affected individuals (III:3, III:4, IV:4 and IV:5). Representation of multi-generation pedigree of alpha-mannosidosis phenotype showing the autosomal pattern of the probands and siblings. Pakistani pedigree with alpha-mannosidosis, presented with pictorial genotypes which cover a nucleotide region of 9.4 Mb at chromosome 19 encompassing the disease locus (dashed blue boxed region).
DNA sequencing shows mutation in alpha-mannosidosis family. Electropherograms of sequencing represents (a) affected individuals (III:3, III:4, IV:4 and IV:5) were displayed to be homozygous for the MAN2B1variant c.2710A>T; p.904Thr>Ser (indicated), (b) heterozygous parents for MAN2B1 variant c.2710A>T; p.904Thr>Ser, while and (c) unaffected sibling were wild-type.
The characterization of MAN2B1 protein for MAN2B1 mutation. In wild-type protein sequence, the amino acid Thr 904 established a hydrogen bond to amino acid Arg 916 residue in the same vicinity (a) while, the mutant sequence has loss the hydrogen bonding (b).