Linkage analysis Dotaz Zobrazit nápovědu
WHO EHG ; 95.26
136 s.
- Konspekt
- Veřejné zdraví a hygiena
- NLK Obory
- environmentální vědy
OBJECTIVE: To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. PATIENTS AND METHODS: We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. RESULTS: Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. CONCLUSION: Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion.
- MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza genetika MeSH
- genetická vazba MeSH
- genetické markery MeSH
- genetické testování metody MeSH
- haplotypy MeSH
- konexiny genetika MeSH
- lidé MeSH
- mutace MeSH
- preimplantační diagnóza metody MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- alfa-amylasy * izolace a purifikace krev moč MeSH
- epidemiologické studie MeSH
- genetická vazba genetika MeSH
- genetické markery genetika MeSH
- genetický výzkum * MeSH
- lékařská genetika metody MeSH
- lidé MeSH
- lidské chromozomy, pár 1 enzymologie genetika MeSH
- pankreas enzymologie metabolismus MeSH
- polymorfismus genetický * genetika MeSH
- rodina etnologie MeSH
- rodokmen MeSH
- sliny enzymologie metabolismus MeSH
- statistika jako téma MeSH
- typy dědičnosti genetika MeSH
- Check Tag
- lidé MeSH
382 s.
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
Cadherins and protocadherins are cell adhesion proteins that play an important role in neuronal migration, differentiation and synaptogenesis, properties that make them targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Consequently, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider. One such set of candidate genes is the 5q31-linked PCDH family, which consists of more than 50 exons encoding three related, though distinct family members--alpha, beta, and gamma--which can generate thousands of different protocadherin proteins through alternative promoter usage and cis-alternative splicing. In this study, we focused on a SNP, rs31745, which is located in a putative PCDHalpha enhancer mapped by ChIP-chip using antibodies to covalently modified histone H3. A striking increase in homozygotes for the minor allele at this locus was detected in patients with BD. Molecular analysis revealed that the SNP causes allele-specific changes in binding to a brain protein. The findings suggest that the 5q31-linked PCDH locus should be more thoroughly considered as a disease-susceptibility locus in psychiatric disorders.
Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species.
- MeSH
- Anopheles klasifikace genetika MeSH
- chromozomální inverze * MeSH
- jednonukleotidový polymorfismus MeSH
- molekulární evoluce MeSH
- populační genetika metody MeSH
- sekvenční analýza DNA MeSH
- shluková analýza MeSH
- Smegmamorpha klasifikace genetika MeSH
- vazebná nerovnováha * MeSH
- výpočetní biologie metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- MeSH
- dospělí MeSH
- fertilizace in vitro MeSH
- genetická vazba MeSH
- genetické nemoci vázané na chromozom X * diagnóza genetika prevence a kontrola MeSH
- haplotypy MeSH
- kohortové studie MeSH
- lidé MeSH
- mikrosatelitní repetice MeSH
- mutace MeSH
- preimplantační diagnóza * metody MeSH
- přenos embrya MeSH
- reprodukovatelnost výsledků MeSH
- retrospektivní studie MeSH
- techniky amplifikace nukleových kyselin MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
